Inhibition of TGFβ Signaling Promotes Ground State Pluripotency

Overview

Journal Stem Cell Rev Rep

Publisher Springer

Specialty Cell Biology

Date 2013 Sep 17

PMID 24036899

Citations 32

Authors

Seyedeh-Nafiseh Hassani

Mehdi Totonchi

Ali Sharifi-Zarchi

Sepideh Mollamohammadi

Mohammad Pakzad

Sharif Moradi

Azam Samadian

Najmehsadat Masoudi

Shahab Mirshahvaladi

Ali Farrokhi

Boris Greber

Marcos J Arauzo-Bravo

Davood Sabour

Mehdi Sadeghi

Ghasem Hosseini Salekdeh

Hamid Gourabi

Hans R Scholer

Hossein Baharvand

Affiliations

Soon will be listed here.

Abstract

Embryonic stem (ES) cells are considered to exist in a ground state if shielded from differentiation triggers. Here we show that FGF4 and TGFβ signaling pathway inhibitors, designated R2i, not only provide the ground state pluripotency in production and maintenance of naïve ES cells from blastocysts of different mouse strains, but also maintain ES cells with higher genomic integrity following long-term cultivation compared with the chemical inhibition of the FGF4 and GSK3 pathways, known as 2i. Global transcriptome analysis of the ES cells highlights augmented BMP4 signaling pathway. The crucial role of the BMP4 pathway in maintaining the R2i ground state pluripotency is demonstrated by BMP4 receptor suppression, resulting in differentiation and cell death. In conclusion, by inhibiting TGFβ and FGF signaling pathways, we introduce a novel defined approach to efficiently establish the ground state pluripotency.

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