Suppression of the ERK-SRF Axis Facilitates Somatic Cell Reprogramming

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2018 Feb 24

PMID 29472703

Citations 12

Authors

Sejong Huh

Hwa-Ryung Song

Geuk-Rae Jeong

Hyejin Jang

Nan-Hee Seo

Ju-Hyun Lee

Ji-Yeun Yi

Byongsun Lee

Hyun Woo Choi

Jeong Tae Do

Jin-Su Kim

Soo-Hong Lee

Jae-Won Jung

Taekyu Lee

Jaekyung Shim

Myung-Kwan Han

Tae-Hee Lee

Affiliations

Soon will be listed here.

Abstract

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.

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