ESRG

Embryonic stem cell-related gene protein (hES cell-related gene protein) [HESRG]

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MYC Releases Early Reprogrammed Human Cells from Proliferation Pause via Retinoblastoma Protein Inhibition.

PubMed

Full text

Here, we report that MYC rescues early human cells undergoing reprogramming from a proliferation pause induced by OCT3/4, SOX2, and KLF4 (OSK). We identified ESRG as a marker of early reprogramming cells that is expressed as early as day 3 after OSK induction. On day 4, ESRG positive ( ) cells converted to a [[TRA]]-1-60 ( ) intermediate state. These early ESRG ( ) or [[TRA]]-1-60 ( ) cells showed a proliferation pause due to increased p16INK4A and p21 and decreased endogenous MYC caused by OSK. Exogenous MYC did not enhance the appearance of initial reprogramming cells but instead reactivated their proliferation and improved reprogramming efficiency. MYC increased expression of LIN41, which potently suppressed p21 post-transcriptionally. MYC suppressed p16 INK4A. These changes inactivated retinoblastoma protein (RB) and reactivated proliferation. The RB-regulated proliferation pause does not occur in immortalized fibroblasts, leading to high reprogramming efficiency even without exogenous MYC.

MeSH Terms

Antigens, Surface
Cell Line
Cell Proliferation
Cellular Reprogramming
Cyclin-Dependent Kinase Inhibitor p16
Humans
Induced Pluripotent Stem Cells
Phosphorylation
Proteoglycans
Proto-Oncogene Proteins c-myc
RNA Interference
RNA, Small Interfering
Retinoblastoma Protein
Transcription Factors
Tripartite Motif Proteins
Ubiquitin-Protein Ligases

Keywords

LIN41
MYC
immortalization
induced pluripotent stem cell
pluripotency
post-transcriptional regulation
proliferation
reprogramming
senescence