Abstract
A unique kind of pluripotent cell, i.e., Induced pluripotent stem cells (iPSCs), now being targeted
for iPSC synthesis, are produced by reprogramming animal and human differentiated cells (with no
change in genetic makeup for the sake of high efficacy iPSCs formation). The conversion of specific cells
to iPSCs has revolutionized stem cell research by making pluripotent cells more controllable for regenerative
therapy. For the past 15 years, somatic cell reprogramming to pluripotency with force expression of
specified factors has been a fascinating field of biomedical study. For that technological primary viewpoint
reprogramming method, a cocktail of four transcription factors (TF) has required: Kruppel-like factor
4 (KLF4), four-octamer binding protein 34 (OCT3/4), MYC and SOX2 (together referred to as
OSKM) and host cells. IPS cells have great potential for future tissue replacement treatments because of
their ability to self-renew and specialize in all adult cell types, although factor-mediated reprogramming
mechanisms are still poorly understood medically. This technique has dramatically improved performance
and efficiency, making it more useful in drug discovery, disease remodeling, and regenerative medicine.
Moreover, in these four TF cocktails, more than 30 reprogramming combinations were proposed, but for
reprogramming effectiveness, only a few numbers have been demonstrated for the somatic cells of humans
and mice. Stoichiometry, a combination of reprogramming agents and chromatin remodeling compounds,
impacts kinetics, quality, and efficiency in stem cell research.
Graphical Abstract
[44]
Bhinge AA. A functional genomics approach to map transcriptional and post-transcriptional gene regulatory network 2009.
[45]
Class I. USPC AN Patent application title: SUPER-ENHANCERS AND METHODS OF USE THEREOF Inventors: Denes Hnisz (Cambridge, MA, US) Brian Abraham (Cambridge, MA, US) Tong Ihn Lee (Somerville, MA, US) Richard A Young (Weston, MA, US). Richard A. Young: Weston, MA, US 2014.
[61]
Davies K. Regulation of Stomatal Development Initiation and Cell Fate Transitions by the bHLH Transcription Factor Speechless. PhD Dissertation Stanford University 2014.
[62]
Chen JX, et al. Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5 Circulation research 2012; 111(1): 50-5.
[76]
Xie G, Lee JE, McKernan K, et al. (2020) MLL3/MLL4 methyltransferase activities regulate embryonic stem cell differentiation independent of enhancer H3K4me1. bioRxiv 2020; 09
[81]
Bernatavichute YV. Mechanisms of CMT3 activation and histone methylation in Arabidopsis thaliana. PhD Dissertation Los Angeles: University of California 2009.
[86]
Jamaladdin SJ. Investigating the physiological role of HDAC1 and HDAC2 in embryonic stem cells. PhD Dissertation University of Leicester 2016.
[89]
Baas R. Mechanisms controlling SMAD-dependent transcription and chromatin modification. Utrecht University 2017.
[99]
Parry A, Rulands S, Reik W. (2021); Active turnover of DNA methylation during cell fate decisions. Natture Reviews Genetics 22(1): 59-66.
[110]
Liu MY. Deciphering the tetrad of epigenetic cytosine modifications 2016.
[117]
Ringrose L. Epigenetics and Systems Biology. Academic Press 2017.
[191]
Aschheim K. Making neurons with microRNAs. Nat Biotechnol 2011; 29(8): 721-2.
[192]
Jayawardena T, Egemnazarov B, Finch E, Zhang L, Payne J, Pandya K. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 2012; 110(11): 1465-73.
[207]
Zhou H. Dissecting transcriptional control by Klf4 in somatic cell reprogramming UCLA Electronic Theses and Dissertations. Los Angeles University of California 2017.