生物
调节器
祖细胞
细胞生物学
干细胞
祖细胞
肠嗜铬样细胞
细胞分化
胃酸
内分泌学
分泌物
遗传学
基因
作者
Mahliyah Adkins-Threats,Sumimasa Arimura,Yang-Zhe Huang,Margarita Divenko,Sarah Q. To,Hua Mao,Yongji Zeng,Jenie Yoonoo Hwang,Joseph Burclaff,Shilpa Jain,Jason C. Mills
标识
DOI:10.1016/j.stem.2024.04.016
摘要
Parietal cells (PCs) produce gastric acid to kill pathogens and aid digestion. Dysregulated PC census is common in disease, yet how PCs differentiate is unclear. Here, we identify the PC progenitors arising from isthmal stem cells, using mouse models and human gastric cells, and show that they preferentially express cell-metabolism regulator and orphan nuclear receptor Estrogen-related receptor gamma (Esrrg, encoding ERRγ). Esrrg expression facilitated the tracking of stepwise molecular, cellular, and ultrastructural stages of PC differentiation. EsrrgP2ACreERT2 lineage tracing revealed that Esrrg expression commits progenitors to differentiate into mature PCs. scRNA-seq indicated the earliest Esrrg+ PC progenitors preferentially express SMAD4 and SP1 transcriptional targets and the GTPases regulating acid-secretion signal transduction. As progenitors matured, ERRγ-dependent metabolic transcripts predominated. Organoid and mouse studies validated the requirement of ERRγ for PC differentiation. Our work chronicles stem cell differentiation along a single lineage in vivo and suggests ERRγ as a therapeutic target for PC-related disorders.
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