Biology subjects

Srinivas, G.

Publications and source records attributed to Srinivas, G..

2 recordsLinked to original sources

bioRxiv2023

Derivation of trophoblast stem cells unveils unrestrained potential of mouse ESCs and epiblast

mESCs and epiblast are considered to follow strict lineage adherence and lack the potential to contribute to trophoectoderm. Here, we report the derivation of trophoblast stem cells (ESTS) from the mESCs. The single-cell transcriptome and molecular characterization of ESTS show similarity with TSCs. They efficiently integrate into the TE compartment of the blastocyst and contribute to the placenta during development. We discovered GSK3{beta} as a critical regulator of the TE fate of ESCs. It plays a vital stage-specific role during ESTS derivation. We further show {beta}-CATENIN and an intron-I regulatory element of Cdx2 are essential for the TE fate of ESCs. We further show that the mouse epiblast can readily differentiate into TE lineage. In contrast to the paradigm of the restricted potential of pluripotent ESCs and epiblast, our data shows that murine ESCs and epiblast have the unrestrained developmental potential for extraembryonic lineages.

developmental biology↗

bioRxiv2021

FGF/ERK autocrine signaling is enhanced by NANOG in a subpopulation of pluripotent stem cells to execute autoregulation and induce heterogeneity

The self-renewal and differentiation potential of Embryonic stem cells (ESCs) is maintained by the regulated expression of core pluripotency factors. The expression level of core pluripotency factor Nanog is tightly regulated by a negative feedback autorepression loop. However, it remains unclear how the ESCs perceive the NANOG levels and execute autorepression. Here, we show that a dose-dependent induction of Fgfbp1 and Fgfr2 by NANOG activates an autocrine mediated ERK signaling in high-Nanog cells to trigger autorepression. pERK recruits NONO to Nanog locus to repress transcription by preventing POL2 loading. The Nanog autorepression process establishes a self-perpetuating NANOG-pERK reciprocal regulatory circuit. We further demonstrate that the reciprocal regulatory circuit induces the pERK heterogeneity and ERK signaling dynamics in pluripotent stem cells.

cell biology↗