BMP4 signaling plays critical roles in self-renewal of R2i mouse embryonic stem cells

نویسندگانSara Taleahmad, Ali Salari, Azam Samadian, Se Hyun Chae, Daehee Hwang, Bonghee Lee, Delger Bayarsaikhan, Govigerel Bayarsaikhan, Jaesuk Lee, Ji Hwan Park, Seyedeh-Nafiseh Hassani, Hossein Baharvand, Ghasem Hosseini Salekdeh
نشریهBiochemical and Biophysical Research Communications
ضریب تاثیر (IF)3
نوع مقالهOriginal Research
تاریخ انتشار20 August 2022
رتبه نشریهISI
نوع نشریهالکترونیکی
کشور محل چاپآرژانتین

چکیده مقاله

Abstract

Mouse embryonic stem cells (mESCs) can be maintained in a pluripotent state under R2i culture conditions that inhibit the TGF-β and ERK signaling pathways. BMP4 is another member of the TGF-β family that plays a crucial role in maintaining the pluripotency state of mESCs. It has been reported that inhibition of BMP4 caused the death of R2i-grown cells. In this study, we used the loss-of-function approach to investigate the role of BMP4 signaling in mESC self-renewal. Inhibition of this pathway with Noggin and dorsomorphin, two bone morphogenetic protein (BMP) antagonists, elicited a quick death of the R2i-grown cells. We showed that the canonical pathway of BMP4 (BMP/SMAD) was dispensable for self-renewal and maintaining pluripotency of these cells. Transcriptome analysis of the BMPi-treated cells revealed that the p53 signaling and two adhesion (AD) and apoptotic mitochondrial change (MT) pathways could be involved in the cell death of the BMPi-treated cells. According to our results, inhibition of BMP4 signaling caused a decrease in cell adhesion and ECM detachment, which triggered anoikis in the R2i-grown cells. Altogether, these findings demonstrate that endogenous BMP signaling is required for the survival of mESCs under the R2i condition.

Graphical abstract

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