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LIN28A inhibited DUSP family phosphatases and activated MAPK signaling pathway to maintain pluripotency in porcine induced pluripotent stem cells

ABSTRACT: LIN28A, an RNA-binding protein, plays an important role in porcine induced pluripotent stem cells (piPSCs). However, the molecular mechanism of LIN28A maintaining pluripotency in piPSCs remains unclear. The aim of this study was to explore the functions of LIN28A in piPSCs. Here we explored the functions of LIN28A in piPSCs by overexpressing and knocking down LIN28A. We performed total RNA sequencing (RNA-seq) on piPSCs and the expression levels of relevant-genes were detected by qRT-PCR, western blot and immunofluorescence staining. The proliferation ability of piPSCs was related to the expression level of LIN28A and the proliferation ability decreased when LIN28A was knocked down. When the expression level of LIN28A was lower than 20% compared with the negative control (shNC) group, the pluripotency of piPSCs would disappear and differentiate to the neuroectoderm. We also found that LIN28A inhibited the expression levels of DUSP (dual-specificity phosphatases) family phosphatases and then activated mitogen-activated protein kinases (MAPK) signaling pathway. This work revealed that LIN28A activated MAPK signaling pathway to maintain the pluripotency and proliferation ability of piPSCs. Our results provided a new resource for exploring the functions of LIN28A in piPSCs.

ORGANISM(S): Sus scrofa

PROVIDER: GSE168591 | GEO | 2024/03/09

REPOSITORIES: GEO

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LIN28A inhibited DUSP family phosphatases and activated MAPK signaling pathway to maintain pluripotency in porcine induced pluripotent stem cells

Project description:LIN28A inhibited DUSP family phosphatases and activated MAPK signaling pathway to maintain pluripotency in porcine induced pluripotent stem cells

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ESRRB Facilitates the Conversion of Trophoblast-like Stem Cells from Induced Pluripotent Stem cells by Directly Regulating KRT8 and CDX2

Project description:Porcine induced pluripotent stem cells (piPSCs) could serve as a great model system for human stem cell pre-clinical research. However, the pluripotency gene network of piPSCs, especially the function for the core transcription factor ESRRB, was poorly understood. Here, we constructed ESRRB-overexpressing piPSCs (ESRRB-piPSCs). Compared with the control piPSCs (CON-piPSCs), the ESRRB-piPSCs showed flat, monolayered colony morphology. Moreover, the ESRRB-piPSCs showed greater chimeric capacity into trophectoderm than CON-piPSCs. We found that ESRRB could directly regulate the expressions of trophoblast stem cell (TSC)-specific markers, including KRT8, KRT18 and CDX2, through binding to their promoter regions. Mutational analysis proved that the N-terminus zinc finger domain is indispensable for ESRRB to regulate the TSC markers. Furthermore, this regulation needs the participation of OCT4. Accordingly, the cooperation between ESRRB and OCT4 facilitates the conversion from pluripotent state to the trophoblast-like state.

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Overlapping and distinct roles of LIN28 paralogs in reprogramming and stem cell metabolism

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Lin28A binds active promoters and recruits Tet1 to regulate gene expression

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