In-depth analysis of proteomic and genomic fluctuations during the time course of human embryonic stem cells directed differentiation into beta cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE158617 | GEO | 2020/09/28
REPOSITORIES: GEO
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Project description:Pluripotent stem cells (PSC) endocrine differentiation at a large scale allows sampling of
transcriptome and proteome with phosphoproteome (proteoform) at specific time points. We describe the dynamic time course of changes in cells undergoing directed beta cell differentiation and show target proteins or previously unknown phosphorylation of critical proteins in pancreas development, NKX6.1, and Chromogranin A (CHGA). We describe fluctuations in the correlation between gene expression, its protein abundance, and phosphorylation, which follow differentiation protocol perturbations of cell fates at all stages to id entify proteoform profiles. Our computational modeling recognizes outliers on a phenomic landscape of endocrine differentiation, and we outline several new biological pathways involved. We also suggest that non correlating proteins abundances or new phosphorylation motifs of NKX6.1 and CHGA point to new signaling pathways that may play an essential role in beta cell development.
| MSV000086154 | MassIVE
Project description:In-depth analysis of proteomic and genomic fluctuations during the time course of human embryonic stem cells directed differentiation into beta cells
| PRJNA665986 | ENA
Project description:SOX2 and OCT4 are pioneer transcription factors playing a key role in embryonic stem (ES) cell self-renewal and differentiation. How temporal fluctuations in their expression levels bias lineage commitment is unknown. Here we generated knock-in reporter fusion ES cell lines allowing to monitor endogenous SOX2 and OCT4 protein fluctuations in living cells and to determine their impact on mesendodermal and neuroectodermal commitment. We found that small differences in SOX2 and OCT4 levels impact cell fate commitment in G1 but not in S phase. Elevated SOX2 levels modestly increased neuroectodermal commitment and decreased mesendodermal commitment upon directed differentiation. In contrast, elevated OCT4 levels strongly biased ES cells towards both neuroectodermal and mesendodermal fates. Using ATAC-seq on ES cells gated for different endogenous SOX2 and OCT4 levels, we found that high OCT4 levels increased chromatin accessibility at differentiation-associated enhancers. This suggests that small endogenous fluctuations of pioneer transcription factors can bias cell fate decisions by concentration-dependent priming of differentiation-associated enhancers.
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