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Updated: Jun 26, 2025

Mouse- and Human-derived Primary Gastric Epithelial Monolayer Culture for the Study of Regeneration
Published on: May 7, 2018
Metabolic regulator ERRγ governs gastric stem cell differentiation into acid-secreting parietal cells
Mahliyah Adkins-Threats1, Sumimasa Arimura2, Yang-Zhe Huang2
1Section of Gastroenterology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Division of Biomedical and Biological Sciences, Washington University, St. Louis, MO 63130, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Abstract:
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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