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In-depth analysis of proteomic and genomic fluctuations during the time course of human embryonic stem cells directed differentiation into beta cells

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dmitry Shvartsman

PROVIDER: MSV000086154 | MassIVE |

SECONDARY ACCESSION(S): PXD021521

REPOSITORIES: MassIVE

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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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