生物
嗜铬粒蛋白A
细胞分化
蛋白质组学
转录组
蛋白质组
干细胞
计算生物学
胚胎干细胞
诱导多能干细胞
定向微分
肠内分泌细胞
细胞生物学
生物信息学
基因表达
基因
遗传学
内分泌系统
免疫学
激素
生物化学
免疫组织化学
作者
Bogdan Budnik,Juerg R. Straubhaar,John M. Neveu,Dmitry Shvartsman
出处
期刊:Proteomics
[Wiley]
日期:2022-01-29
卷期号:: 2100265-2100265
被引量:2
标识
DOI:10.1002/pmic.202100265
摘要
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, protein abundance, and phosphorylation, following differentiation protocol perturbations at all stages to identify proteoform profiles. Our modeling recognizes outliers on a phenomic landscape of endocrine differentiation, and we describe new biological pathways involved. We have validated our proteomic data by analyzing independent single-cell RNAseq datasets for in-vitro pancreatic islet production and corroborated our findings for several proteins suggestive as targets for future research. The single-cell analysis combined with proteoform data places new protein targets within the specific time point and at the specific pancreatic lineage of differentiating stem cells. We 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. We present our findings for the research community's use to improve endocrine differentiation protocols and developmental studies.
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