| First Author | Adkins-Threats M | Year | 2024 |
| Journal | Cell Stem Cell | Volume | 31 |
| Issue | 6 | Pages | 886-903.e8 |
| PubMed ID | 38733994 | Mgi Jnum | J:349437 |
| Mgi Id | MGI:7645116 | Doi | 10.1016/j.stem.2024.04.016 |
| Citation | Adkins-Threats M, et al. (2024) Metabolic regulator ERRgamma governs gastric stem cell differentiation into acid-secreting parietal cells. Cell Stem Cell |
| abstractText | 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 ERRgamma). Esrrg expression facilitated the tracking of stepwise molecular, cellular, and ultrastructural stages of PC differentiation. Esrrg(P2ACreERT2) 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, ERRgamma-dependent metabolic transcripts predominated. Organoid and mouse studies validated the requirement of ERRgamma for PC differentiation. Our work chronicles stem cell differentiation along a single lineage in vivo and suggests ERRgamma as a therapeutic target for PC-related disorders. |
