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 - http://www.scopus.com/inward/record.url?scp=84893739522&partnerID=8YFLogxK
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 -