美国贝勒医学院Jason C. Mills研究小组发现，代谢调节因子ERRγ控制胃干细胞向分泌胃酸的顶叶细胞分化。2024年5月10日，《细胞—干细胞》杂志在线发表了这项成果。

据悉，PC产生胃酸，以杀死病原体并帮助消化。PC失调在疾病中很常见，但PC如何分化尚不清楚。

附：英文原文

Title: Metabolic regulator ERRγ governs gastric stem cell differentiation into acid-secreting parietal cells

Author: Mahliyah Adkins-Threats, Sumimasa Arimura, Yang-Zhe Huang, Margarita Divenko, Sarah To, Heather Mao, Yongji Zeng, Jenie Y. Hwang, Joseph R. Burclaff, Shilpa Jain, Jason C. Mills

Issue&Volume: 2024-05-10

Abstract: Parietal cells (PCs) produce gastric acid to kill pathogens and aid digestion. DysregulatedPC census is common in disease, yet how PCs differentiate is unclear. Here, we identifythe PC progenitors arising from isthmal stem cells, using mouse models and human gastriccells, and show that they preferentially express cell-metabolism regulator and orphannuclear receptor Estrogen-related receptor gamma (Esrrg, encoding ERRγ). Esrrg expression facilitated the tracking of stepwise molecular, cellular, and ultrastructuralstages of PC differentiation. EsrrgP2ACreERT2 lineage tracing revealed that Esrrg expression commits progenitors to differentiate into mature PCs. scRNA-seq indicatedthe earliest Esrrg+ PC progenitors preferentially express SMAD4 and SP1 transcriptional targets andthe GTPases regulating acid-secretion signal transduction. As progenitors matured,ERRγ-dependent metabolic transcripts predominated. Organoid and mouse studies validatedthe requirement of ERRγ for PC differentiation. Our work chronicles stem cell differentiationalong a single lineage in vivo and suggests ERRγ as a therapeutic target for PC-related disorders.

DOI: 10.1016/j.stem.2024.04.016

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00143-7