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

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Apr 12

PMID 29641997

Citations 12

Authors

Tim A Rand

Kenta Sutou

Koji Tanabe

Daeun Jeong

Masaki Nomura

Fumiyo Kitaoka

Emi Tomoda

Megumi Narita

Michiko Nakamura

Masahiro Nakamura

Akira Watanabe

Eric Rulifson

Shinya Yamanaka

Kazutoshi Takahashi

Affiliations

Soon will be listed here.

Abstract

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.

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