Single-cell RNA Sequencing: In-depth Decoding of Heart Biology and Cardiovascular Diseases

Zhongli       Chen; Liang       Wei; Firat       Duru; Liang       Chen
Abstract

Background: The cardiac system is a combination of a complex structure, various cells, and versatile specified functions and sophisticated regulatory mechanisms. Moreover, cardiac diseases that encompass a wide range of endogenous conditions, remain a serious health burden worldwide. Recent genome-wide profiling techniques have taken the lead in uncovering a new realm of cell types and molecular programs driving physiological and pathological processes in various organs and diseases. In particular, the emerging technique single-cell RNA sequencing dominates a breakthrough in decoding the cell heterogeneity, phenotype transition, and developmental dynamics in cardiovascular science.
Conclusion: Herein, we review recent advances in single cellular studies of cardiovascular system and summarize new insights provided by single-cell RNA sequencing in heart developmental sciences, stem-cell researches as well as normal or disease-related working mechanisms.
Keywords: Singe-cell RNA sequencing, cardiovascular disease, cardiogenesis, stem cells, vascular system, heart transcriptome.
Graphical Abstract

[1] 
Kent, A.F. Researches on the structure and function of the mammalian heart. J. Physiol.,  1893, 14(4-5), i2-i254.
[http://dx.doi.org/10.1113/jphysiol.1893.sp000451] [PMID: 16992052] 
[2] 
Monney, P.; Piccini, D.; Rutz, T.; Vincenti, G.; Coppo, S.; Koestner, S.C.; Sekarski, N.; Di Bernardo, S.; Bouchardy, J.; Stuber, M.; Schwitter, J. Single centre experience of the application of self navigated 3D whole heart cardiovascular magnetic resonance for the assessment of cardiac anatomy in congenital heart disease. J. Cardiovasc. Magn. Reson.,  2015, 17(1), 55.
[http://dx.doi.org/10.1186/s12968-015-0156-7] [PMID: 26156377] 
[3] 
Madonna, R.; Van Laake, L.W.; Botker, H.E.; Davidson, S.M.; De Caterina, R.; Engel, F.B.; Eschenhagen, T.; Fernandez-Aviles, F.; Hausenloy, D.J.; Hulot, J-S.; Lecour, S.; Leor, J.; Menasché, P.; Pesce, M.; Perrino, C.; Prunier, F.; Van Linthout, S.; Ytrehus, K.; Zimmermann, W.H.; Ferdinandy, P.; Sluijter, J.P.G. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure. Cardiovasc. Res.,  2019, 115(3), 488-500.
[http://dx.doi.org/10.1093/cvr/cvz010] [PMID: 30657875] 
[4] 
Suthahar, N.; Meijers, W.C.; Silljé, H.H.W.; de Boer, R.A. From inflammation to fibrosis-molecular and cellular mechanisms of myocardial tissue remodelling and perspectives on differential treatment opportunities. Curr. Heart Fail. Rep.,  2017, 14(4), 235-250.
[http://dx.doi.org/10.1007/s11897-017-0343-y] [PMID: 28707261] 
[5] 
Fotiou, E.; Williams, S.; Martin-Geary, A.; Robertson, D.L.; Tenin, G.; Hentges, K.E.; Keavney, B. Integration of large-scale genomic data sources with evolutionary history reveals novel genetic loci for congenital heart disease. Circ Genom Precis Med,  2019, 12(10), 442-451.
[PMID: 31613678] 
[6] 
Abraham, G.; Havulinna, A.S.; Bhalala, O.G.; Byars, S.G.; De Livera, A.M.; Yetukuri, L.; Tikkanen, E.; Perola, M.; Schunkert, H.; Sijbrands, E.J.; Palotie, A.; Samani, N.J.; Salomaa, V.; Ripatti, S.; Inouye, M. Genomic prediction of coronary heart disease. Eur. Heart J.,  2016, 37(43), 3267-3278.
[http://dx.doi.org/10.1093/eurheartj/ehw450] [PMID: 27655226] 
[7] 
Hashimoto, H.; Olson, E.N.; Bassel-Duby, R. Therapeutic approaches for cardiac regeneration and repair. Nat. Rev. Cardiol.,  2018, 15(10), 585-600.
[http://dx.doi.org/10.1038/s41569-018-0036-6] [PMID: 29872165] 
[8] 
Wagner, J.; Rapsomaniki, M.A.; Chevrier, S.; Anzeneder, T.; Langwieder, C.; Dykgers, A.; Rees, M.; Ramaswamy, A.; Muenst, S.; Soysal, S.D.; Jacobs, A.; Windhager, J.; Silina, K.; van den Broek, M.; Dedes, K.J.; Rodríguez Martínez, M.; Weber, W.P.; Bodenmiller, B. A Single-cell atlas of the tumor and immune ecosystem of human breast cancer. Cell,  2019, 177(5), 1330-1345.e18.
[http://dx.doi.org/10.1016/j.cell.2019.03.005] [PMID: 30982598] 
[9] 
Susaki, E.A.; Ueda, H.R. Whole-body and whole-organ clearing and imaging techniques with single-cell resolution: toward organism-level systems biology in mammals. Cell Chem. Biol.,  2016, 23(1), 137-157.
[http://dx.doi.org/10.1016/j.chembiol.2015.11.009] [PMID: 26933741] 
[10] 
Potter, S.S. Single-cell RNA sequencing for the study of development, physiology and disease. Nat. Rev. Nephrol.,  2018, 14(8), 479-492.
[http://dx.doi.org/10.1038/s41581-018-0021-7] [PMID: 29789704] 
[11] 
Reyfman, P.A.; Walter, J.M.; Joshi, N.; Anekalla, K.R.; McQuattie-Pimentel, A.C.; Chiu, S.; Fernandez, R.; Akbarpour, M.; Chen, C.I.; Ren, Z.; Verma, R.; Abdala-Valencia, H.; Nam, K.; Chi, M.; Han, S.; Gonzalez-Gonzalez, F.J.; Soberanes, S.; Watanabe, S.; Williams, K.J.N.; Flozak, A.S.; Nicholson, T.T.; Morgan, V.K.; Winter, D.R.; Hinchcliff, M.; Hrusch, C.L.; Guzy, R.D.; Bonham, C.A.; Sperling, A.I.; Bag, R.; Hamanaka, R.B.; Mutlu, G.M.; Yeldandi, A.V.; Marshall, S.A.; Shilatifard, A.; Amaral, L.A.N.; Perlman, H.; Sznajder, J.I.; Argento, A.C.; Gillespie, C.T.; Dematte, J.; Jain, M.; Singer, B.D.; Ridge, K.M.; Lam, A.P.; Bharat, A.; Bhorade, S.M.; Gottardi, C.J.; Budinger, G.R.S.; Misharin, A.V. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am. J. Respir. Crit. Care Med.,  2019, 199(12), 1517-1536.
[http://dx.doi.org/10.1164/rccm.201712-2410OC] [PMID: 30554520] 
[12] 
Zhu, Y.; Sousa, A.M.M.; Gao, T.; Skarica, M.; Li, M.; Santpere, G.; Esteller-Cucala, P.; Juan, D.; Ferrández-Peral, L.; Gulden, F.O.; Yang, M.; Miller, D.J.; Marques-Bonet, T.; Imamura Kawasawa, Y.; Zhao, H.; Sestan, N. Spatiotemporal transcriptomic divergence across human and macaque brain development. Science,  2018, 362(6420)eaat8077
[http://dx.doi.org/10.1126/science.aat8077] [PMID: 30545855] 
[13] 
Vanlandewijck, M.; He, L.; Mäe, M.A.; Andrae, J.; Ando, K.; Del Gaudio, F.; Nahar, K.; Lebouvier, T.; Laviña, B.; Gouveia, L.; Sun, Y.; Raschperger, E.; Räsänen, M.; Zarb, Y.; Mochizuki, N.; Keller, A.; Lendahl, U.; Betsholtz, C. A molecular atlas of cell types and zonation in the brain vasculature. Nature,  2018, 554(7693), 475-480.
[http://dx.doi.org/10.1038/nature25739] [PMID: 29443965] 
[14] 
Tasic, B.; Yao, Z.; Graybuck, L.T.; Smith, K.A.; Nguyen, T.N.; Bertagnolli, D.; Goldy, J.; Garren, E.; Economo, M.N.; Viswanathan, S.; Penn, O.; Bakken, T.; Menon, V.; Miller, J.; Fong, O.; Hirokawa, K.E.; Lathia, K.; Rimorin, C.; Tieu, M.; Larsen, R.; Casper, T.; Barkan, E.; Kroll, M.; Parry, S.; Shapovalova, N.V.; Hirschstein, D.; Pendergraft, J.; Sullivan, H.A.; Kim, T.K.; Szafer, A.; Dee, N.; Groblewski, P.; Wickersham, I.; Cetin, A.; Harris, J.A.; Levi, B.P.; Sunkin, S.M.; Madisen, L.; Daigle, T.L.; Looger, L.; Bernard, A.; Phillips, J.; Lein, E.; Hawrylycz, M.; Svoboda, K.; Jones, A.R.; Koch, C.; Zeng, H. Shared and distinct transcriptomic cell types across neocortical areas. Nature,  2018, 563(7729), 72-78.
[http://dx.doi.org/10.1038/s41586-018-0654-5] [PMID: 30382198] 
[15] 
Tabula, M.C. Overall coordination; Logistical coordination; Organ collection and processing; Library preparation and sequencing; Computational data analysis; Cell type annotation; Writing group; Supplemental text writing group; Principal investigators. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature,  2018, 562(7727), 367-372.
[http://dx.doi.org/10.1038/s41586-018-0590-4] [PMID: 30283141] 
[16] 
Popescu, D.M.; Botting, R.A.; Stephenson, E.; Green, K.; Webb, S.; Jardine, L.; Calderbank, E.F.; Polanski, K.; Goh, I.; Efremova, M.; Acres, M.; Maunder, D.; Vegh, P.; Gitton, Y.; Park, J.E.; Vento-Tormo, R.; Miao, Z.; Dixon, D.; Rowell, R.; McDonald, D.; Fletcher, J.; Poyner, E.; Reynolds, G.; Mather, M.; Moldovan, C.; Mamanova, L.; Greig, F.; Young, M.D.; Meyer, K.B.; Lisgo, S.; Bacardit, J.; Fuller, A.; Millar, B.; Innes, B.; Lindsay, S.; Stubbington, M.J.T.; Kowalczyk, M.S.; Li, B.; Ashenberg, O.; Tabaka, M.; Dionne, D.; Tickle, T.L.; Slyper, M.; Rozenblatt-Rosen, O.; Filby, A.; Carey, P.; Villani, A.C.; Roy, A.; Regev, A.; Chédotal, A.; Roberts, I.; Göttgens, B.; Behjati, S.; Laurenti, E.; Teichmann, S.A.; Haniffa, M. Decoding human fetal liver haematopoiesis. Nature,  2019, 574(7778), 365-371.
[http://dx.doi.org/10.1038/s41586-019-1652-y] [PMID: 31597962] 
[17] 
Park, J.; Shrestha, R.; Qiu, C.; Kondo, A.; Huang, S.; Werth, M.; Li, M.; Barasch, J.; Suszták, K. Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science,  2018, 360(6390), 758-763.
[http://dx.doi.org/10.1126/science.aar2131] [PMID: 29622724] 
[18] 
Merrick, D.; Sakers, A.; Irgebay, Z.; Okada, C.; Calvert, C.; Morley, M.P.; Percec, I.; Seale, P. Identification of a mesenchymal progenitor cell hierarchy in adipose tissue. Science,  2019, 364(6438)eaav2501
[http://dx.doi.org/10.1126/science.aav2501] [PMID: 31023895] 
[19] 
Halpern, K.B.; Shenhav, R.; Matcovitch-Natan, O.; Toth, B.; Lemze, D.; Golan, M.; Massasa, E.E.; Baydatch, S.; Landen, S.; Moor, A.E.; Brandis, A.; Giladi, A.; Avihail, A.S.; David, E.; Amit, I.; Itzkovitz, S. Single-cell spatial reconstruction reveals global division of labour in the mammalian liver. Nature,  2017, 542(7641), 352-356.
[http://dx.doi.org/10.1038/nature21065] [PMID: 28166538] 
[20] 
Haber, A.L.; Biton, M.; Rogel, N.; Herbst, R.H.; Shekhar, K.; Smillie, C.; Burgin, G.; Delorey, T.M.; Howitt, M.R.; Katz, Y.; Tirosh, I.; Beyaz, S.; Dionne, D.; Zhang, M.; Raychowdhury, R.; Garrett, W.S.; Rozenblatt-Rosen, O.; Shi, H.N.; Yilmaz, O.; Xavier, R.J.; Regev, A. A single-cell survey of the small intestinal epithelium. Nature,  2017, 551(7680), 333-339.
[http://dx.doi.org/10.1038/nature24489] [PMID: 29144463] 
[21] 
Enge, M.; Arda, H.E.; Mignardi, M.; Beausang, J.; Bottino, R.; Kim, S.K.; Quake, S.R. Single-cell analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns. Cell,  2017, 171(2), 321-330.e14.
[http://dx.doi.org/10.1016/j.cell.2017.09.004] 
[22] 
Bornstein, C.; Nevo, S.; Giladi, A.; Kadouri, N.; Pouzolles, M.; Gerbe, F.; David, E.; Machado, A.; Chuprin, A.; Tóth, B.; Goldberg, O.; Itzkovitz, S.; Taylor, N.; Jay, P.; Zimmermann, V.S.; Abramson, J.; Amit, I. Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells. Nature,  2018, 559(7715), 622-626.
[http://dx.doi.org/10.1038/s41586-018-0346-1] [PMID: 30022162] 
[23] 
Ayyaz, A.; Kumar, S.; Sangiorgi, B.; Ghoshal, B.; Gosio, J.; Ouladan, S.; Fink, M.; Barutcu, S.; Trcka, D.; Shen, J.; Chan, K.; Wrana, J.L.; Gregorieff, A. Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell. Nature,  2019, 569(7754), 121-125.
[http://dx.doi.org/10.1038/s41586-019-1154-y] [PMID: 31019301] 
[24] 
Arazi, A.; Rao, D.A.; Berthier, C.C.; Davidson, A.; Liu, Y.; Hoover, P.J.; Chicoine, A.; Eisenhaure, T.M.; Jonsson, A.H.; Li, S.; Lieb, D.J.; Zhang, F.; Slowikowski, K.; Browne, E.P.; Noma, A.; Sutherby, D.; Steelman, S.; Smilek, D.E.; Tosta, P.; Apruzzese, W.; Massarotti, E.; Dall’Era, M.; Park, M.; Kamen, D.L.; Furie, R.A.; Payan-Schober, F.; Pendergraft, W.F., III; McInnis, E.A.; Buyon, J.P.; Petri, M.A.; Putterman, C.; Kalunian, K.C.; Woodle, E.S.; Lederer, J.A.; Hildeman, D.A.; Nusbaum, C.; Raychaudhuri, S.; Kretzler, M.; Anolik, J.H.; Brenner, M.B.; Wofsy, D.; Hacohen, N.; Diamond, B. The immune cell landscape in kidneys of patients with lupus nephritis. Nat. Immunol.,  2019, 20(7), 902-914.
[http://dx.doi.org/10.1038/s41590-019-0398-x] [PMID: 31209404] 
[25] 
Aizarani, N.; Saviano, A. Sagar; Mailly, L.; Durand, S.; Herman, J. S.; Pessaux, P.; Baumert, T. F.; Grun, D. A human liver cell atlas reveals heterogeneity and epithelial progenitors. Nature,  2019, 572, 199-204.
[http://dx.doi.org/10.1038/s41586-019-1373-2] 
[26] 
Ackers-Johnson, M.; Tan, W.L.W.; Foo, R.S. Following hearts, one cell at a time: recent applications of single-cell RNA sequencing to the understanding of heart disease. Nat. Commun.,  2018, 9(1), 4434.
[http://dx.doi.org/10.1038/s41467-018-06894-8] [PMID: 30375391] 
[27] 
Zhang, X.; Li, T.; Liu, F.; Chen, Y.; Yao, J.; Li, Z.; Huang, Y.; Wang, J. Comparative analysis of droplet-based ultra-high-throughput single-cell rna-seq systems. Mol. Cell,  2019, 73(1), 130-142.e5.
[28] 
Goldstein, L.D.; Chen, Y.J.; Dunne, J.; Mir, A.; Hubschle, H.; Guillory, J.; Yuan, W.; Zhang, J.; Stinson, J.; Jaiswal, B.; Pahuja, K.B.; Mann, I.; Schaal, T.; Chan, L.; Anandakrishnan, S.; Lin, C.W.; Espinoza, P.; Husain, S.; Shapiro, H.; Swaminathan, K.; Wei, S.; Srinivasan, M.; Seshagiri, S.; Modrusan, Z. Massively parallel nanowell-based single-cell gene expression profiling. BMC Genomics,  2017, 18(1), 519.
[http://dx.doi.org/10.1186/s12864-017-3893-1] [PMID: 28687070] 
[29] 
Han, X.; Wang, R.; Zhou, Y.; Fei, L.; Sun, H.; Lai, S.; Saadatpour, A.; Zhou, Z.; Chen, H.; Ye, F.; Huang, D.; Xu, Y.; Huang, W.; Jiang, M.; Jiang, X.; Mao, J.; Chen, Y.; Lu, C.; Xie, J.; Fang, Q.; Wang, Y.; Yue, R.; Li, T.; Huang, H.; Orkin, S.H.; Yuan, G.C.; Chen, M.; Guo, G. Mapping the mouse cell atlas by microwell-seq. Cell,  2018, 173(5), 1307.
[http://dx.doi.org/10.1016/j.cell.2018.05.012] [PMID: 29775597] 
[30] 
Kwan, K.Y. Single-cell transcriptome analysis of developing and regenerating spiral ganglion neurons. Curr. Pharmacol. Rep.,  2016, 2(5), 211-220.
[http://dx.doi.org/10.1007/s40495-016-0064-z] [PMID: 28758056] 
[31] 
Ziegenhain, C.; Vieth, B.; Parekh, S.; Reinius, B.; Guillaumet-Adkins, A.; Smets, M.; Leonhardt, H.; Heyn, H.; Hellmann, I.; Enard, W. Comparative analysis of single-cell rna sequencing methods. Mol. Cell,  2017, 65(4), 631-643.e4.
[http://dx.doi.org/10.1016/j.molcel.2017.01.023] 
[32] 
Picelli, S.; Faridani, O.R.; Björklund, A.K.; Winberg, G.; Sagasser, S.; Sandberg, R. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc.,  2014, 9(1), 171-181.
[http://dx.doi.org/10.1038/nprot.2014.006] [PMID: 24385147] 
[33] 
Ziegenhain, C.; Vieth, B.; Parekh, S.; Reinius, B.; Guillaumet-Adkins, A.; Smets, M.; Leonhardt, H.; Heyn, H.; Hellmann, I.; Enard, W. Comparative analysis of single-cell RNA sequencing methods. Mol. Cell,  2017, 65(4), 631-643.e4.
[http://dx.doi.org/10.1016/j.molcel.2017.01.023] 
[34] 
Nomura, S.; Satoh, M.; Fujita, T.; Higo, T.; Sumida, T.; Ko, T.; Yamaguchi, T.; Tobita, T.; Naito, A.T.; Ito, M.; Fujita, K.; Harada, M.; Toko, H.; Kobayashi, Y.; Ito, K.; Takimoto, E.; Akazawa, H.; Morita, H.; Aburatani, H.; Komuro, I. Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure. Nat. Commun.,  2018, 9(1), 4435.
[http://dx.doi.org/10.1038/s41467-018-06639-7] [PMID: 30375404] 
[35] 
Wang, Y.J.; Schug, J.; Lin, J.; Wang, Z.; Kossenkov, A.; Kaestner, K.H.; Consortium, H. Comparative analysis of commercially available single-cell RNA sequencing platforms for their performance in complex human tissues. bioRxiv,  2019, •••541433
[36] 
Wang, L.; Yu, P.; Zhou, B.; Song, J.; Li, Z.; Zhang, M.; Guo, G.; Wang, Y.; Chen, X.; Han, L.; Hu, S. Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function. Nat. Cell Biol.,  2020, 22(1), 108-119.
[http://dx.doi.org/10.1038/s41556-019-0446-7] [PMID: 31915373] 
[37] 
DeLaughter, D.M.; Bick, A.G.; Wakimoto, H.; McKean, D.; Gorham, J.M.; Kathiriya, I.S.; Hinson, J.T.; Homsy, J.; Gray, J.; Pu, W.; Bruneau, B.G.; Seidman, J.G.; Seidman, C.E. Single-cell resolution of temporal gene expression during heart development. Dev. Cell,  2016, 39(4), 480-490.
[http://dx.doi.org/10.1016/j.devcel.2016.10.001] [PMID: 27840107] 
[38] 
Li, G.; Xu, A.; Sim, S.; Priest, J.R.; Tian, X.; Khan, T.; Quertermous, T.; Zhou, B.; Tsao, P.S.; Quake, S.R.; Wu, S.M. Transcriptomic profiling maps anatomically patterned subpopulations among single embryonic cardiac cells. Dev. Cell,  2016, 39(4), 491-507.
[http://dx.doi.org/10.1016/j.devcel.2016.10.014] [PMID: 27840109] 
[39] 
Gladka, M.M.; Molenaar, B.; de Ruiter, H.; van der Elst, S.; Tsui, H.; Versteeg, D.; Lacraz, G.P.A.; Huibers, M.M.H.; van Oudenaarden, A.; van Rooij, E. Single-cell sequencing of the healthy and diseased heart reveals cytoskeleton-associated protein 4 as a new modulator of fibroblasts activation. Circulation,  2018, 138(2), 166-180.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.030742] [PMID: 29386203] 
[40] 
Ackers-Johnson, M.; Li, P.Y.; Holmes, A.P.; O’Brien, S.M.; Pavlovic, D.; Foo, R.S. A simplified, langendorff-free method for concomitant isolation of viable cardiac myocytes and nonmyocytes from the adult mouse heart. Circ. Res.,  2016, 119(8), 909-920.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309202] [PMID: 27502479] 
[41] 
Guo, G.R.; Chen, L.; Rao, M.; Chen, K.; Song, J.P.; Hu, S.S. A modified method for isolation of human cardiomyocytes to model cardiac diseases. J. Transl. Med.,  2018, 16(1), 288.
[http://dx.doi.org/10.1186/s12967-018-1649-6] [PMID: 30348184] 
[42] 
Lake, B.B.; Ai, R.; Kaeser, G.E.; Salathia, N.S.; Yung, Y.C.; Liu, R.; Wildberg, A.; Gao, D.; Fung, H.L.; Chen, S.; Vijayaraghavan, R.; Wong, J.; Chen, A.; Sheng, X.; Kaper, F.; Shen, R.; Ronaghi, M.; Fan, J.B.; Wang, W.; Chun, J.; Zhang, K. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science,  2016, 352(6293), 1586-1590.
[http://dx.doi.org/10.1126/science.aaf1204] [PMID: 27339989] 
[43] 
Habib, N.; Avraham-Davidi, I.; Basu, A.; Burks, T.; Shekhar, K.; Hofree, M.; Choudhury, S.R.; Aguet, F.; Gelfand, E.; Ardlie, K.; Weitz, D.A.; Rozenblatt-Rosen, O.; Zhang, F.; Regev, A. Massively parallel single-nucleus RNA-seq with DroNc-seq. Nat. Methods,  2017, 14(10), 955-958.
[http://dx.doi.org/10.1038/nmeth.4407] [PMID: 28846088] 
[44] 
Lake, B.B.; Codeluppi, S.; Yung, Y.C.; Gao, D.; Chun, J.; Kharchenko, P.V.; Linnarsson, S.; Zhang, K. A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA. Sci. Rep.,  2017, 7(1), 6031.
[http://dx.doi.org/10.1038/s41598-017-04426-w] [PMID: 28729663] 
[45] 
Wu, H.; Kirita, Y.; Donnelly, E.L.; Humphreys, B.D. Advantages of single-nucleus over single-cell RNA sequencing of adult kidney: rare cell types and novel cell states revealed in fibrosis. J. Am. Soc. Nephrol.,  2019, 30(1), 23-32.
[http://dx.doi.org/10.1681/ASN.2018090912] [PMID: 30510133] 
[46] 
Hu, P.; Liu, J.; Zhao, J.; Wilkins, B.J.; Lupino, K.; Wu, H.; Pei, L. Single-nucleus transcriptomic survey of cell diversity and functional maturation in postnatal mammalian hearts. Genes Dev.,  2018, 32(19-20), 1344-1357.
[http://dx.doi.org/10.1101/gad.316802.118] [PMID: 30254108] 
[47] 
See, K.; Tan, W.L.W.; Lim, E.H.; Tiang, Z.; Lee, L.T.; Li, P.Y.Q.; Luu, T.D.A.; Ackers-Johnson, M.; Foo, R.S. Single cardiomyocyte nuclear transcriptomes reveal a lincRNA-regulated de-differentiation and cell cycle stress-response in vivo. Nat. Commun.,  2017, 8(1), 225.
[http://dx.doi.org/10.1038/s41467-017-00319-8] [PMID: 28790305] 
[48] 
Zhang, Y.; Gago-Lopez, N.; Li, N.; Zhang, Z.; Alver, N.; Liu, Y.; Martinson, A.M.; Mehri, A.; MacLellan, W.R. Single-cell imaging and transcriptomic analyses of endogenous cardiomyocyte dedifferentiation and cycling. Cell Discov.,  2019, 5, 30.
[http://dx.doi.org/10.1038/s41421-019-0095-9] [PMID: 31231540] 
[49] 
Linscheid, N.; Logantha, S.J.R.J.; Poulsen, P.C.; Zhang, S.; Schrölkamp, M.; Egerod, K.L.; Thompson, J.J.; Kitmitto, A.; Galli, G.; Humphries, M.J.; Zhang, H.; Pers, T.H.; Olsen, J.V.; Boyett, M.; Lundby, A. Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking. Nat. Commun.,  2019, 10(1), 2889.
[http://dx.doi.org/10.1038/s41467-019-10709-9] [PMID: 31253831] 
[50] 
Tucker, N.R.; Chaffin, M.; Fleming, S.J.; Hall, A.W.; Parsons, V.A.; Bedi, K.; Akkad, A-D.; Herndon, C.N.; Arduini, A.; Papangeli, I.; Roselli, C.; Aguet, F.; Choi, S.H.; Ardlie, K.G.; Babadi, M.; Margulies, K.B.; Stegmann, C.M.; Ellinor, P.T. Transcriptional and cellular diversity of the human heart. bioRxiv, 2020.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.045401] 
[51] 
Chaudhry, F.; Isherwood, J.; Bawa, T.; Patel, D.; Gurdziel, K.; Lanfear, D.E.; Ruden, D.M.; Levy, P.D. Single-cell RNA sequencing of the cardiovascular system: new looks for old diseases. Front. Cardiovasc. Med.,  2019, 6, 173.
[http://dx.doi.org/10.3389/fcvm.2019.00173] [PMID: 31921894] 
[52] 
Skelly, D.A.; Squiers, G.T.; McLellan, M.A.; Bolisetty, M.T.; Robson, P.; Rosenthal, N.A.; Pinto, A.R. Single-cell transcriptional profiling reveals cellular diversity and intercommunication in the mouse heart. Cell Rep.,  2018, 22(3), 600-610.
[http://dx.doi.org/10.1016/j.celrep.2017.12.072] [PMID: 29346760] 
[53] 
Lakatta, E.G.; DiFrancesco, D. What keeps us ticking: a funny current, a calcium clock, or both? J. Mol. Cell. Cardiol.,  2009, 47(2), 157-170.
[http://dx.doi.org/10.1016/j.yjmcc.2009.03.022] [PMID: 19361514] 
[54] 
Vidal, R.; Wagner, J.U.G.; Braeuning, C.; Fischer, C.; Patrick, R.; Tombor, L.; Muhly-Reinholz, M.; John, D.; Kliem, M.; Conrad, T.; Guimarães-Camboa, N.; Harvey, R.; Dimmeler, S.; Sauer, S. Transcriptional heterogeneity of fibroblasts is a hallmark of the aging heart. JCI Insight,  2019, 4(22)131092
[http://dx.doi.org/10.1172/jci.insight.131092] [PMID: 31723062] 
[55] 
Jensen, B.; Wang, T.; Christoffels, V.M.; Moorman, A.F.M. Evolution and development of the building plan of the vertebrate heart. Biochim. Biophys. Acta,  2013, 1833(4), 783-794.
[http://dx.doi.org/10.1016/j.bbamcr.2012.10.004] [PMID: 23063530] 
[56] 
Pervolaraki, E.; Dachtler, J.; Anderson, R.A.; Holden, A.V. The developmental transcriptome of the human heart. Sci. Rep.,  2018, 8(1), 15362.
[http://dx.doi.org/10.1038/s41598-018-33837-6] [PMID: 30337648] 
[57] 
Schmidt, C. Single-cell transcriptomics in embryology: implications for cardiovascular science. Cardiovasc. Res.,  2018, 114(12), e87-e88.
[http://dx.doi.org/10.1093/cvr/cvy193] [PMID: 31346599] 
[58] 
Li, G.; Tian, L.; Goodyer, W.; Kort, E.J.; Buikema, J.W.; Xu, A.; Wu, J.C.; Jovinge, S.; Wu, S.M. Single cell expression analysis reveals anatomical and cell cycle-dependent transcriptional shifts during heart development. Development,  2019, 146(12)dev173476
[http://dx.doi.org/10.1242/dev.173476] [PMID: 31142541] 
[59] 
Cui, Y.; Zheng, Y.; Liu, X.; Yan, L.; Fan, X.; Yong, J.; Hu, Y.; Dong, J.; Li, Q.; Wu, X.; Gao, S.; Li, J.; Wen, L.; Qiao, J.; Tang, F. Single-cell transcriptome analysis maps the developmental track of the human heart. Cell Rep.,  2019, 26(7), 1934-1950.e5.
[http://dx.doi.org/10.1016/j.celrep.2019.01.079] 
[60] 
Asp, M.; Giacomello, S.; Larsson, L.; Wu, C.; Furth, D.; Qian, X.; Wardell, E.; Custodio, J.; Reimegard, J.; Salmen, F.; Osterholm, C.; Stahl, P.L.; Sundstrom, E.; Akesson, E.; Bergmann, O.; Bienko, M.; Mansson-Broberg, A.; Nilsson, M.; Sylven, C.; Lundeberg, J. A spatiotemporal organ-wide gene expression and cell atlas of the developing human heart. Cell,  2019, 179(7), 1647-1660.e19.
[http://dx.doi.org/10.1016/j.cell.2019.11.025] 
[61] 
Xiao, Y.; Hill, M.C.; Zhang, M.; Martin, T.J.; Morikawa, Y.; Wang, S.; Moise, A.R.; Wythe, J.D.; Martin, J.F. Hippo signaling plays an essential role in cell state transitions during cardiac fibroblast development. Dev. Cell,  2018, 45(2), 153-169.e6.
[http://dx.doi.org/10.1016/j.devcel.2018.03.019] 
[62] 
Hulin, A.; Hortells, L.; Gomez-Stallons, M.V.; O’Donnell, A.; Chetal, K.; Adam, M.; Lancellotti, P.; Oury, C.; Potter, S.S.; Salomonis, N.; Yutzey, K.E. Maturation of heart valve cell populations during postnatal remodeling. Development,  2019, 146(12)dev173047
[http://dx.doi.org/10.1242/dev.173047] [PMID: 30796046] 
[63] 
Sereti, K.I.; Nguyen, N.B.; Kamran, P.; Zhao, P.; Ranjbarvaziri, S.; Park, S.; Sabri, S.; Engel, J.L.; Sung, K.; Kulkarni, R.P.; Ding, Y.; Hsiai, T.K.; Plath, K.; Ernst, J.; Sahoo, D.; Mikkola, H.K.A.; Iruela-Arispe, M.L.; Ardehali, R. Analysis of cardiomyocyte clonal expansion during mouse heart development and injury. Nat. Commun.,  2018, 9(1), 754.
[http://dx.doi.org/10.1038/s41467-018-02891-z] [PMID: 29467410] 
[64] 
Xiong, H.; Luo, Y.; Yue, Y.; Zhang, J.; Ai, S.; Li, X.; Wang, X.; Zhang, Y-L.; Wei, Y.; Li, H-H.; Hu, X.; Li, C.; He, A. Single-cell transcriptomics reveals chemotaxis-mediated intraorgan crosstalk during cardiogenesis. Circ. Res.,  2019, 125(4), 398-410.
[http://dx.doi.org/10.1161/CIRCRESAHA.119.315243] [PMID: 31221018] 
[65] 
Lescroart, F.; Wang, X.; Lin, X.; Swedlund, B.; Gargouri, S.; Sànchez-Dànes, A.; Moignard, V.; Dubois, C.; Paulissen, C.; Kinston, S.; Göttgens, B.; Blanpain, C. Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq. Science,  2018, 359(6380), 1177-1181.
[http://dx.doi.org/10.1126/science.aao4174] [PMID: 29371425] 
[66] 
Sahara, M.; Santoro, F.; Sohlmér, J.; Zhou, C.; Witman, N.; Leung, C.Y.; Mononen, M.; Bylund, K.; Gruber, P.; Chien, K.R. Population and single-cell analysis of human cardiogenesis reveals unique LGR5 ventricular progenitors in embryonic outflow tract. Dev. Cell,  2019, 48(4), 475-490.e7.
[http://dx.doi.org/10.1016/j.devcel.2019.01.005] [PMID: 30713072] 
[67] 
Jia, G.; Preussner, J.; Chen, X.; Guenther, S.; Yuan, X.; Yekelchyk, M.; Kuenne, C.; Looso, M.; Zhou, Y.; Teichmann, S.; Braun, T. Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement. Nat. Commun.,  2018, 9(1), 4877.
[http://dx.doi.org/10.1038/s41467-018-07307-6] [PMID: 30451828] 
[68] 
de Soysa, T.Y.; Ranade, S.S.; Okawa, S.; Ravichandran, S.; Huang, Y.; Salunga, H.T.; Schricker, A.; Del Sol, A.; Gifford, C.A.; Srivastava, D. Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects. Nature,  2019, 572(7767), 120-124.
[http://dx.doi.org/10.1038/s41586-019-1414-x] [PMID: 31341279] 
[69] 
Goodyer, W.R.; Beyersdorf, B.M.; Paik, D.T.; Tian, L.; Li, G.; Buikema, J.W.; Chirikian, O.; Choi, S.; Venkatraman, S.; Adams, E.L.; Tessier-Lavigne, M.; Wu, J.C.; Wu, S.M. Transcriptomic profiling of the developing cardiac conduction system at single-cell resolution. Circ. Res.,  2019, 125(4), 379-397.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.314578] [PMID: 31284824] 
[70] 
Suryawanshi, H.; Clancy, R.; Morozov, P.; Halushka, M.K.; Buyon, J.P.; Tuschl, T. Cell atlas of the fetal human heart and implications for autoimmune-mediated congenital heart block. Cardiovasc. Res.,  2020, 116(8), 1446-1457.
[http://dx.doi.org/10.1093/cvr/cvz257] [PMID: 31589297] 
[71] 
Pries, A.R.; Reglin, B. Coronary microcirculatory pathophysiology: can we afford it to remain a black box? Eur. Heart J.,  2017, 38(7), 478-488.
[PMID: 26843279] 
[72] 
Montezano, A.C.; Sarafian, R.D.; Neves, K.B.; Rios, F.J.; Passaglia, P.; Camargo, L.L.; Haddow, L.; Ford, T.J.; Dunne, M.; Alves-Lopes, R. Role of Nox5 in systemic vascular dysfunction in ischemic heart disease. Hypertension, 2019. 74(Suppl_1), A089.
[73] 
Schiffrin, E.L. Hypertension in 2017: Novel mechanisms of hypertension and vascular dysfunction. Nat. Rev. Nephrol.,  2018, 14(2), 73-74.
[http://dx.doi.org/10.1038/nrneph.2017.178] [PMID: 29292372] 
[74] 
Selthofer-Relatic, K.; Mihalj, M.; Kibel, A.; Stupin, A.; Stupin, M.; Jukic, I.; Koller, A.; Drenjancevic, I. Coronary microcirculatory dysfunction in human cardiomyopathies. Cardiol. Rev.,  2017, 25(4), 165-178.
[http://dx.doi.org/10.1097/CRD.0000000000000140] [PMID: 28574936] 
[75] 
Niwa, K. Aortic dilatation in complex congenital heart disease. Cardiovasc. Diagn. Ther.,  2018, 8(6), 725-738.
[http://dx.doi.org/10.21037/cdt.2018.12.05] [PMID: 30740320] 
[76] 
Elworthy, S.; Savage, A.M.; Wilkinson, R.N.; Malicki, J.J.; Chico, T.J.A. The role of endothelial cilia in postembryonic vascular development. Dev. Dyn.,  2019, 248(6), 410-425.
[http://dx.doi.org/10.1002/dvdy.40] [PMID: 30980582] 
[77] 
Stark, R.; Grzelak, M.; Hadfield, J. RNA sequencing: the teenage years. Nat. Rev. Genet.,  2019, 20(11), 631-656.
[http://dx.doi.org/10.1038/s41576-019-0150-2] [PMID: 31341269] 
[78] 
Kulkarni, A.; Anderson, A.G.; Merullo, D.P.; Konopka, G. Beyond bulk: a review of single cell transcriptomics methodologies and applications. Curr. Opin. Biotechnol.,  2019, 58, 129-136.
[http://dx.doi.org/10.1016/j.copbio.2019.03.001] [PMID: 30978643] 
[79] 
Su, T.; Stanley, G.; Sinha, R.; D’Amato, G.; Das, S.; Rhee, S.; Chang, A.H.; Poduri, A.; Raftrey, B.; Dinh, T.T.; Roper, W.A.; Li, G.; Quinn, K.E.; Caron, K.M.; Wu, S.; Miquerol, L.; Butcher, E.C.; Weissman, I.; Quake, S.; Red-Horse, K. Single-cell analysis of early progenitor cells that build coronary arteries. Nature,  2018, 559(7714), 356-362.
[http://dx.doi.org/10.1038/s41586-018-0288-7] [PMID: 29973725] 
[80] 
Liu, X.; Chen, W.; Li, W.; Li, Y.; Priest, J.R.; Zhou, B.; Wang, J.; Zhou, Z. Single-cell RNA-seq of the developing cardiac outflow tract reveals convergent development of the vascular smooth muscle cells. Cell Rep.,  2019, 28(5), 1346-1361.e4.
[http://dx.doi.org/10.1016/j.celrep.2019.06.092] [PMID: 31365875] 
[81] 
Kalluri, A.S.; Vellarikkal, S.K.; Edelman, E.R.; Nguyen, L.; Subramanian, A.; Ellinor, P.T.; Regev, A.; Kathiresan, S.; Gupta, R.M. Single-cell analysis of the normal mouse aorta reveals functionally distinct endothelial cell populations. Circulation,  2019, 140(2), 147-163.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038362] [PMID: 31146585] 
[82] 
Lukowski, S.W.; Patel, J.; Andersen, S.B.; Sim, S.L.; Wong, H.Y.; Tay, J.; Winkler, I.; Powell, J.E.; Khosrotehrani, K. Single-cell transcriptional profiling of aortic endothelium identifies a hierarchy from endovascular progenitors to differentiated cells. Cell Rep.,  2019, 27(9), 2748-2758.e3.
[http://dx.doi.org/10.1016/j.celrep.2019.04.102] 
[83] 
Dobnikar, L.; Taylor, A.L.; Chappell, J.; Oldach, P.; Harman, J.L.; Oerton, E.; Dzierzak, E.; Bennett, M.R.; Spivakov, M.; Jørgensen, H.F. Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels. Nat. Commun.,  2018, 9(1), 4567.
[http://dx.doi.org/10.1038/s41467-018-06891-x] [PMID: 30385745] 
[84] 
Musunuru, K.; Sheikh, F.; Gupta, R.M.; Houser, S.R.; Maher, K.O.; Milan, D.J.; Terzic, A.; Wu, J.C. American Heart Association Council on Functional Genomics and Translational Biology; Council on Cardiovascular Disease in the Young; and Council on Cardiovascular and Stroke Nursing. Induced pluripotent stem cells for cardiovascular disease modeling and precision medicine: a scientific statement from the American Heart Association. Circ. Genom Precis. Med.,  2018, 11(1)e000043
[http://dx.doi.org/10.1161/HCG.0000000000000043] [PMID: 29874173] 
[85] 
Hnatiuk, A.; Mercola, M. Stars in the night sky: iPSC-CMs return the patient context to drug screening. Cell Stem Cell,  2019, 24(4), 506-507.
[http://dx.doi.org/10.1016/j.stem.2019.03.013] [PMID: 30951657] 
[86] 
Gintant, G.; Fermini, B.; Stockbridge, N.; Strauss, D. The evolving roles of human iPSC-derived CMs in drug safety and discovery. Cell Stem Cell,  2017, 21(1), 14-17.
[http://dx.doi.org/10.1016/j.stem.2017.06.005] [PMID: 28686863] 
[87] 
Jang, S.; Collin de l’Hortet, A.; Soto-Gutierrez, A. Induced pluripotent stem cell-derived endothelial cells: overview, current advances, applications, and future directions. Am. J. Pathol.,  2019, 189(3), 502-512.
[http://dx.doi.org/10.1016/j.ajpath.2018.12.004] [PMID: 30653953] 
[88] 
Lin, Y.; Gil, C-H.; Yoder, M.C. Differentiation, evaluation, and application of human induced pluripotent stem cell-derived endothelial cells. Arterioscler. Thromb. Vasc. Biol.,  2017, 37(11), 2014-2025.
[http://dx.doi.org/10.1161/ATVBAHA.117.309962] [PMID: 29025705] 
[89] 
Germanguz, I.; Sedan, O.; Zeevi-Levin, N.; Shtrichman, R.; Barak, E.; Ziskind, A.; Eliyahu, S.; Meiry, G.; Amit, M.; Itskovitz-Eldor, J.; Binah, O. Molecular characterization and functional properties of cardiomyocytes derived from human inducible pluripotent stem cells. J. Cell. Mol. Med.,  2011, 15(1), 38-51.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00996.x] [PMID: 20041972] 
[90] 
Almeida, S.O.; Skelton, R.J.; Adigopula, S.; Ardehali, R. Arrhythmia in stem cell transplantation. Card. Electrophysiol. Clin.,  2015, 7(2), 357-370.
[http://dx.doi.org/10.1016/j.ccep.2015.03.012] [PMID: 26002399] 
[91] 
Ni, N.C.; Li, R-K.; Weisel, R.D. The promise and challenges of cardiac stem cell therapy, Seminars in thoracic and cardiovascular surgery; Elsevier, 2014, pp. 44-52.
[92] 
Friedman, C.E.; Nguyen, Q.; Lukowski, S.W.; Helfer, A.; Chiu, H.S.; Miklas, J.; Levy, S.; Suo, S.; Han, J.J.; Osteil, P.; Peng, G.; Jing, N.; Baillie, G.J.; Senabouth, A.; Christ, A.N.; Bruxner, T.J.; Murry, C.E.; Wong, E.S.; Ding, J.; Wang, Y.; Hudson, J.; Ruohola-Baker, H.; Bar-Joseph, Z.; Tam, P.P.L.; Powell, J.E.; Palpant, N.J. Single-cell transcriptomic analysis of cardiac differentiation from human PSCs reveals HOPX-dependent cardiomyocyte maturation. Cell Stem Cell,  2018, 23(4), 586-598.e8.
[93] 
Churko, J.M.; Garg, P.; Treutlein, B.; Venkatasubramanian, M.; Wu, H.; Lee, J.; Wessells, Q.N.; Chen, S.Y.; Chen, W.Y.; Chetal, K.; Mantalas, G.; Neff, N.; Jabart, E.; Sharma, A.; Nolan, G.P.; Salomonis, N.; Wu, J.C. Defining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis. Nat. Commun.,  2018, 9(1), 4906.
[http://dx.doi.org/10.1038/s41467-018-07333-4] [PMID: 30464173] 
[94] 
McCracken, I.R.; Taylor, R.S.; Kok, F.O.; de la Cuesta, F.; Dobie, R.; Henderson, B.E.P.; Mountford, J.C.; Caudrillier, A.; Henderson, N.C.; Ponting, C.P.; Baker, A.H. Transcriptional dynamics of pluripotent stem cell-derived endothelial cell differentiation revealed by single-cell RNA sequencing. Eur. Heart J.,  2019, 41(9), 1024-1036.
[http://dx.doi.org/10.1093/eurheartj/ehz351] [PMID: 31242503] 
[95] 
Paik, D.T.; Tian, L.; Lee, J.; Sayed, N.; Chen, I.Y.; Rhee, S.; Rhee, J.W.; Kim, Y.; Wirka, R.C.; Buikema, J.W.; Wu, S.M.; Red-Horse, K.; Quertermous, T.; Wu, J.C. Large-scale single-cell RNA-seq reveals molecular signatures of heterogeneous populations of human induced pluripotent stem cell-derived endothelial cells. Circ. Res.,  2018, 123(4), 443-450.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.312913] [PMID: 29986945] 
[96] 
Liu, M.; Gomez, D. Smooth muscle cell phenotypic diversity. Arterioscler. Thromb. Vasc. Biol.,  2019, 39(9), 1715-1723.
[http://dx.doi.org/10.1161/ATVBAHA.119.312131] [PMID: 31340668] 
[97] 
Sussman, M.A. Cardiac nonmyocyte subpopulations: a secular congregation. Regen. Med.,  2019, 14(6), 489-494.
[http://dx.doi.org/10.2217/rme-2019-0053] [PMID: 31115258] 
[98] 
Schultze, J.L. Myocardial infarction cell by cell. Nat. Immunol.,  2019, 20(1), 7-9.
[http://dx.doi.org/10.1038/s41590-018-0277-x] [PMID: 30538327] 
[99] 
Nahrendorf, M. Myeloid cells in cardiovascular organs. J. Intern. Med.,  2019, 285(5), 491-502.
[http://dx.doi.org/10.1111/joim.12844] [PMID: 30585362] 
[100] 
Bennett, M.R.; Sinha, S.; Owens, G.K. Vascular smooth muscle cells in atherosclerosis. Circ. Res.,  2016, 118(4), 692-702.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306361] [PMID: 26892967] 
[101] 
Wirka, R.C.; Wagh, D.; Paik, D.T.; Pjanic, M.; Nguyen, T.; Miller, C.L.; Kundu, R.; Nagao, M.; Coller, J.; Koyano, T.K.; Fong, R.; Woo, Y.J.; Liu, B.; Montgomery, S.B.; Wu, J.C.; Zhu, K.; Chang, R.; Alamprese, M.; Tallquist, M.D.; Kim, J.B.; Quertermous, T. Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis. Nat. Med.,  2019, 25(8), 1280-1289.
[http://dx.doi.org/10.1038/s41591-019-0512-5] [PMID: 31359001] 
[102] 
Kim, K.; Shim, D.; Lee, J.S.; Zaitsev, K.; Williams, J.W.; Kim, K.W.; Jang, M.Y.; Seok Jang, H.; Yun, T.J.; Lee, S.H.; Yoon, W.K.; Prat, A.; Seidah, N.G.; Choi, J.; Lee, S.P.; Yoon, S.H.; Nam, J.W.; Seong, J.K.; Oh, G.T.; Randolph, G.J.; Artyomov, M.N.; Cheong, C.; Choi, J.H. Transcriptome analysis reveals nonfoamy rather than foamy plaque macrophages are proinflammatory in atherosclerotic murine models. Circ. Res.,  2018, 123(10), 1127-1142.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.312804] [PMID: 30359200] 
[103] 
Cochain, C.; Vafadarnejad, E.; Arampatzi, P.; Pelisek, J.; Winkels, H.; Ley, K.; Wolf, D.; Saliba, A.E.; Zernecke, A. Single-cell RNA-Seq reveals the transcriptional landscape and heterogeneity of aortic macrophages in murine atherosclerosis. Circ. Res.,  2018, 122(12), 1661-1674.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.312509] [PMID: 29545365] 
[104] 
Gu, W.; Ni, Z.; Tan, Y.Q.; Deng, J.; Zhang, S.J.; Lv, Z.C.; Wang, X.J.; Chen, T.; Zhang, Z.; Hu, Y.; Jing, Z.C.; Xu, Q. Adventitial cell atlas of wt (wild type) and ApoE (Apolipoprotein E)-deficient mice defined by single-cell RNA sequencing. Arterioscler. Thromb. Vasc. Biol.,  2019, 39(6), 1055-1071.
[105] 
Winkels, H.; Ehinger, E.; Vassallo, M.; Buscher, K.; Dinh, H.Q.; Kobiyama, K.; Hamers, A.A.J.; Cochain, C.; Vafadarnejad, E.; Saliba, A.E.; Zernecke, A.; Pramod, A.B.; Ghosh, A.K.; Anto Michel, N.; Hoppe, N.; Hilgendorf, I.; Zirlik, A.; Hedrick, C.C.; Ley, K.; Wolf, D. Atlas of the Immune Cell Repertoire in Mouse Atherosclerosis Defined by Single-Cell RNA-Sequencing and Mass Cytometry. Circ. Res.,  2018, 122(12), 1675-1688.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.312513] [PMID: 29545366] 
[106] 
Ruiz-Villalba, A.; Romero, J.P.; Hernandez, S.C.; Vilas-Zornoza, A.; Fortelny, N.; Castro, L.; Martin-Uriz, P.S.; Lorenzo-Vivas, E.; García-Olloqui, P.; Palacios, M.; Gavira, J.J.; Bastarrika, G.; Janssens, S.; Iglesias, E.; Abizanda, G.; de Morentin, X.M.; Bock, C.; Alignani, D.; Medal, G.; Gomez-Cabrero, D.; Prudovsky, I.; Jin, Y-R.; Ryzhov, S.; Yin, H.; Pelacho, B.; Lindner, V.; Lara-Astiaso, D.; Prósper, F. Single-cell RNA-seq analysis reveals the crucial role of Collagen Triplex Helix Repeat Containing 1 (CTHRC1) cardiac fibroblasts for ventricular remodeling after myocardial infarction. bioRxiv, 2019.643130
[107] 
Li, Z.; Solomonidis, E.G.; Meloni, M.; Taylor, R.S.; Duffin, R.; Dobie, R.; Magalhaes, M.S.; Henderson, B.E.P.; Louwe, P.A.; D’Amico, G.; Hodivala-Dilke, K.M.; Shah, A.M.; Mills, N.L.; Simons, B.D.; Gray, G.A.; Henderson, N.C.; Baker, A.H.; Brittan, M. Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial cells following myocardial infarction. Eur. Heart J.,  2019, 40(30), 2507-2520.
[http://dx.doi.org/10.1093/eurheartj/ehz305] [PMID: 31162546] 
[108] 
Bajpai, G.; Bredemeyer, A.; Li, W.; Zaitsev, K.; Koenig, A.L.; Lokshina, I.; Mohan, J.; Ivey, B.; Hsiao, H-M.; Weinheimer, C.; Kovacs, A.; Epelman, S.; Artyomov, M.; Kreisel, D.; Lavine, K.J. Tissue Resident CCR2- and CCR2+ Cardiac Macrophages Differentially Orchestrate Monocyte Recruitment and Fate Specification Following Myocardial Injury. Circ. Res.,  2019, 124(2), 263-278.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.314028] [PMID: 30582448] 
[109] 
Calcagno, D.M.; Ng, R.P.; Toomu, A.; Zhang, C.; Huang, K.; Aguirre, A.D.; Weissleder, R.; Daniels, L.B.; Fu, Z.; King, K.R. Type I interferon responses to ischemic injury begin in the bone marrow of mice and humans and depend on Tet2, Nrf2, and Irf3. bioRxiv, 2020.765404
[110] 
Vafadarnejad, E.; Rizzo, G.; Krampert, L.; Arampatzi, P.; Nugroho, V.A.; Schulz, D.J.; Roesch, M.; Alayrac, P.; Vilar, J.; Silvestre, J-S. Time-resolved single-cell transcriptomics uncovers dynamics of cardiac neutrophil diversity in murine myocardial infarction. bioRxiv, 2019.738005
[111] 
Kretzschmar, K.; Post, Y.; Bannier-Hélaouët, M.; Mattiotti, A.; Drost, J.; Basak, O.; Li, V.S.W.; van den Born, M.; Gunst, Q.D.; Versteeg, D.; Kooijman, L.; van der Elst, S.; van Es, J.H.; van Rooij, E.; van den Hoff, M.J.B.; Clevers, H. Profiling proliferative cells and their progeny in damaged murine hearts. Proc. Natl. Acad. Sci. USA,  2018, 115(52), E12245-E12254.
[http://dx.doi.org/10.1073/pnas.1805829115] [PMID: 30530645] 
[112] 
Leung, O.M.; Li, J.; Li, X.; Chan, V.W.; Yang, K.Y.; Ku, M.; Ji, L.; Sun, H.; Waldmann, H.; Tian, X.Y.; Huang, Y.; Lau, J.; Zhou, B.; Lui, K.O. Regulatory T cells promote apelin-mediated sprouting angiogenesis in type 2 diabetes. Cell Rep.,  2018, 24(6), 1610-1626.
[http://dx.doi.org/10.1016/j.celrep.2018.07.019] [PMID: 30089270] 
[113] 
Li, J.; Yang, K.Y.; Tam, R.C.Y.; Chan, V.W.; Lan, H.Y.; Hori, S.; Zhou, B.; Lui, K.O. Regulatory T-cells regulate neonatal heart regeneration by potentiating cardiomyocyte proliferation in a paracrine manner. Theranostics,  2019, 9(15), 4324-4341.
[http://dx.doi.org/10.7150/thno.32734] [PMID: 31285764] 
[114] 
Martini, E.; Kunderfranco, P.; Peano, C.; Carullo, P.; Cremonesi, M.; Schorn, T.; Carriero, R.; Termanini, A.; Colombo, F.S.; Jachetti, E.; Panico, C.; Faggian, G.; Fumero, A.; Torracca, L.; Molgora, M.; Cibella, J.; Pagiatakis, C.; Brummelman, J.; Alvisi, G.; Mazza, E.M.C.; Colombo, M.P.; Lugli, E.; Condorelli, G.; Kallikourdis, M. Single-cell sequencing of mouse heart immune infiltrate in pressure overload-driven heart failure reveals extent of immune activation. Circulation,  2019, 140(25), 2089-2107.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.041694] [PMID: 31661975] 
[115] 
Wünnemann, F.; Ta-Shma, A.; Preuss, C.; Leclerc, S.; van Vliet, P.P.; Oneglia, A.; Thibeault, M.; Nordquist, E.; Lincoln, J.; Scharfenberg, F.; Becker-Pauly, C.; Hofmann, P.; Hoff, K.; Audain, E.; Kramer, H-H.; Makalowski, W.; Nir, A.; Gerety, S.S.; Hurles, M.; Comes, J.; Fournier, A.; Osinska, H.; Robins, J.; Pucéat, M.; Elpeleg, O.; Hitz, M-P.; Andelfinger, G. MIBAVA Leducq Consortium principal investigators. Loss of ADAMTS19 causes progressive non-syndromic heart valve disease. Nat. Genet.,  2020, 52(1), 40-47.
[http://dx.doi.org/10.1038/s41588-019-0536-2] [PMID: 31844321] 
[116] 
Cusanovich, D.A.; Hill, A.J.; Aghamirzaie, D.; Daza, R.M.; Pliner, H.A.; Berletch, J.B.; Filippova, G.N.; Huang, X.; Christiansen, L.; DeWitt, W.S.; Lee, C.; Regalado, S.G.; Read, D.F.; Steemers, F.J.; Disteche, C.M.; Trapnell, C.; Shendure, J. A single-cell atlas of in vivo mammalian chromatin accessibility. Cell,  2018, 174(5), 1309-1324.e18.
[http://dx.doi.org/10.1016/j.cell.2018.06.052] 
Cite As
Current Genomics

Single-cell RNA Sequencing: In-depth Decoding of Heart Biology and Cardiovascular Diseases

Abstract

Graphical Abstract
