Inhibition of TGFβ signaling promotes ground state pluripotency

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. Araúzo-Bravo; Davood Sabour; Mehdi Sadeghi; Ghasem Hosseini Salekdeh; Hamid Gourabi; Hans R. Schöler; Hossein Baharvand

doi:10.1007/s12015-013-9473-0

Inhibition of TGFβ signaling promotes ground state pluripotency

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. Araúzo-Bravo, Davood Sabour, Mehdi Sadeghi, Ghasem Hosseini Salekdeh, Hamid Gourabi, Hans R. Schöler, Hossein Baharvand^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

65 Citations (Scopus)

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.

Original language	English
Pages (from-to)	16-30
Number of pages	15
Journal	Stem Cell Reviews and Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1007/s12015-013-9473-0
Publication status	Published - Feb 2014
Externally published	Yes

Bibliographical note

A correction exists for this article and can be found in Stem Cell Reviews and Reports (2022) Vol 18(1) at doi: 10.1007/s12015-021-10268-x

Keywords

Embryonic stem cells
ERK pathway
Ground state pluripotency
TGF-β pathway

Access to Document

10.1007/s12015-013-9473-0

Cite this

Hassani, S. N., Totonchi, M., Sharifi-Zarchi, A., Mollamohammadi, S., Pakzad, M., Moradi, S., Samadian, A., Masoudi, N., Mirshahvaladi, S., Farrokhi, A., Greber, B., Araúzo-Bravo, M. J., Sabour, D., Sadeghi, M., Salekdeh, G. H., Gourabi, H., Schöler, H. R., & Baharvand, H. (2014). Inhibition of TGFβ signaling promotes ground state pluripotency. Stem Cell Reviews and Reports, 10(1), 16-30. https://doi.org/10.1007/s12015-013-9473-0

@article{20d43721eb55403381b4b312ab9feeef,

title = "Inhibition of TGFβ signaling promotes ground state pluripotency",

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 na{\"i}ve 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.",

keywords = "Embryonic stem cells, ERK pathway, Ground state pluripotency, TGF-β pathway",

author = "Hassani, \{Seyedeh Nafiseh\} and Mehdi Totonchi and Ali Sharifi-Zarchi and Sepideh Mollamohammadi and Mohammad Pakzad and Sharif Moradi and Azam Samadian and Najmehsadat Masoudi and Shahab Mirshahvaladi and Ali Farrokhi and Boris Greber and Ara{\'u}zo-Bravo, \{Marcos J.\} and Davood Sabour and Mehdi Sadeghi and Salekdeh, \{Ghasem Hosseini\} and Hamid Gourabi and Sch{\"o}ler, \{Hans R.\} and Hossein Baharvand",

note = "A correction exists for this article and can be found in Stem Cell Reviews and Reports (2022) Vol 18(1) at doi: 10.1007/s12015-021-10268-x",

year = "2014",

month = feb,

doi = "10.1007/s12015-013-9473-0",

language = "English",

volume = "10",

pages = "16--30",

journal = "Stem Cell Reviews and Reports",

issn = "1550-8943",

publisher = "Humana Press Inc.",

number = "1",

}

Hassani, SN, Totonchi, M, Sharifi-Zarchi, A, Mollamohammadi, S, Pakzad, M, Moradi, S, Samadian, A, Masoudi, N, Mirshahvaladi, S, Farrokhi, A, Greber, B, Araúzo-Bravo, MJ, Sabour, D, Sadeghi, M, Salekdeh, GH, Gourabi, H, Schöler, HR & Baharvand, H 2014, 'Inhibition of TGFβ signaling promotes ground state pluripotency', Stem Cell Reviews and Reports, vol. 10, no. 1, pp. 16-30. https://doi.org/10.1007/s12015-013-9473-0

TY - JOUR

T1 - Inhibition of TGFβ signaling promotes ground state pluripotency

AU - Hassani, Seyedeh Nafiseh

AU - Totonchi, Mehdi

AU - Sharifi-Zarchi, Ali

AU - Mollamohammadi, Sepideh

AU - Pakzad, Mohammad

AU - Moradi, Sharif

AU - Samadian, Azam

AU - Masoudi, Najmehsadat

AU - Mirshahvaladi, Shahab

AU - Farrokhi, Ali

AU - Greber, Boris

AU - Araúzo-Bravo, Marcos J.

AU - Sabour, Davood

AU - Sadeghi, Mehdi

AU - Salekdeh, Ghasem Hosseini

AU - Gourabi, Hamid

AU - Schöler, Hans R.

AU - Baharvand, Hossein

N1 - A correction exists for this article and can be found in Stem Cell Reviews and Reports (2022) Vol 18(1) at doi: 10.1007/s12015-021-10268-x

PY - 2014/2

Y1 - 2014/2

N2 - 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.

AB - 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.

KW - Embryonic stem cells

KW - ERK pathway

KW - Ground state pluripotency

KW - TGF-β pathway

UR - https://www.scopus.com/pages/publications/84893739522

UR - https://doi.org/10.1007/s12015-021-10268-x

UR - http://www.scopus.com/inward/record.url?scp=85116749976&partnerID=8YFLogxK

U2 - 10.1007/s12015-013-9473-0

DO - 10.1007/s12015-013-9473-0

M3 - Article

C2 - 24036899

AN - SCOPUS:84893739522

SN - 1550-8943

VL - 10

SP - 16

EP - 30

JO - Stem Cell Reviews and Reports

JF - Stem Cell Reviews and Reports

IS - 1

ER -

Inhibition of TGFβ signaling promotes ground state pluripotency

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this