Figure 1.
SOX9 is expressed in progenitor cells and glandular mucous cells during development and injury. During early development, anti-SOX9 immunohistochemistry marks all gastric progenitors: (A) E13.5 and (B) E15.5. In late gestation or early postnatal life, SOX9 is (C) lost from gastric progenitors near the surface (P0), but (D) still expressed throughout all non–surface-associated progenitors in the gland (P7). (E) In the second week of postnatal life, SOX9 expression at the base becomes less intense and ubiquitous at the base (P14). (F) By P21, SOX9 becomes concentrated in the neck region of mature gastric corpus units. (G) In P28 units, the pattern of SOX9 expression resembles that of adult units, with high expression in mucous neck cells. (H) Representative units after high-dose tamoxifen (HDT) injury at peak metaplasia stages (day 3). High SOX9 expression is observed in the neck and base of these injured units. (I) Representative basal metaplasia from the TxA23 autoimmune gastritis model after 12 weeks. SOX9 strongly marks all inflamed metaplastic cells in these stomachs. Immunofluorescence staining of adult gastric tissue stained with SOX9, a general nuclear marker, and representative markers of (J) prepit/pit cells (KLF4), (K) isthmal cells/proliferative zone (Ki67), (L) mucous neck cells (GS-II), and (M) chief cells (GIF). Nuclear expression of SOX9 is detected in some cells of all lineages, with most SOX9 being in isthmus and neck. (N and O) Analysis of previously published scRNA-seq data collected from homeostasis, acute injury, and chronic inflammatory injury conditions. (N) UMAP (Uniform manifold approximation and projection) unbiased clustering of gastric cell suspensions isolated from healthy BALB/c, HDT, and TxA23 mice colored by cluster identity. (O) Violin plots of Sox9 gene expression levels in all identified clusters of the combined healthy and injured scRNA-seq libraries. During homeostasis (except parietal, tuft, enterochromaffin-like [ECL], and endocrine cells) and both injury conditions (except ECL and endocrine cells), Sox9 messenger RNA is detected in all major gastric lineages, with the highest expression in stem and mucous neck cells and in metaplastic cells. All immunohistochemistry sections were counterstained with hematoxylin. Scale bars: 20 μm.