SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced Metaplasia

Area of Science:

• Gastroenterology
• Developmental Biology
• Cell Biology

Background:

• Gastric injury triggers pyloric metaplasia, characterized by parietal cell death and chief cell reprogramming into spasmolytic polypeptide-expressing metaplasia (SPEM) cells.
• Pyloric metaplasia involves increased proliferation and expansion of mucous lineages, including mucous neck cells and SPEM cells.

Purpose of the Study:

• To investigate the role of SRY-box transcription factor 9 (SOX9) in regulating mucous neck and SPEM cell identity in the stomach.
• To elucidate SOX9's function during gastric development, homeostasis, and injury response.

Main Methods:

• Immunostaining and electron microscopy were employed to analyze SOX9 expression patterns.
• Studies included murine models of gastric development, homeostasis, Sox9 genetic deletion, and targeted misexpression in gastric epithelium and chief cells.

Main Results:

• SOX9 is expressed in gastric progenitors and mature mucous neck cells, with induced expression in SPEM cells after injury.
• Sox9 deficiency in progenitors resulted in a lack of mature mucous neck cells.
• Sox9 misexpression expanded mucous gene expression, while its deletion in chief cells inhibited SPEM reprogramming.

Conclusions:

• SOX9 acts as a master regulator of mucous neck cell differentiation during gastric development.
• SOX9 is essential for the proper reprogramming of chief cells into SPEM cells following gastric injury.