SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced MetaplasiaSummary
Background & Aims: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into prol...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X23001066 |
| _version_ | 1797778398792122368 |
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| author | Spencer G. Willet Nattapon Thanintorn Helen McNeill Sung-Ho Huh David M. Ornitz Won Jae Huh Stella G. Hoft Richard J. DiPaolo Jason C. Mills |
| author_facet | Spencer G. Willet Nattapon Thanintorn Helen McNeill Sung-Ho Huh David M. Ornitz Won Jae Huh Stella G. Hoft Richard J. DiPaolo Jason C. Mills |
| author_sort | Spencer G. Willet |
| collection | DOAJ |
| description | Background & Aims: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into proliferative, mucin-rich spasmolytic polypeptide–expressing metaplasia (SPEM) cells. Overall, pyloric metaplastic units show increased proliferation and specific expansion of mucous lineages, both by proliferation of normal mucous neck cells and recruitment of SPEM cells. Here, we identify Sox9 as a potential gene of interest in the regulation of mucous neck and SPEM cell identity in the stomach. Methods: We used immunostaining and electron microscopy to characterize the expression pattern of SRY-box transcription factor 9 (SOX9) during murine gastric development, homeostasis, and injury in homeostasis, after genetic deletion of Sox9 and after targeted genetic misexpression of Sox9 in the gastric epithelium and chief cells. Results: SOX9 is expressed in all early gastric progenitors and strongly expressed in mature mucous neck cells with minor expression in the other principal gastric lineages during adult homeostasis. After injury, strong SOX9 expression was induced in the neck and base of corpus units in SPEM cells. Adult corpus units derived from Sox9-deficient gastric progenitors lacked normal mucous neck cells. Misexpression of Sox9 during postnatal development and adult homeostasis expanded mucous gene expression throughout corpus units including within the chief cell zone in the base. Sox9 deletion specifically in chief cells blunts their reprogramming into SPEM. Conclusions: Sox9 is a master regulator of mucous neck cell differentiation during gastric development. Sox9 also is required for chief cells to fully reprogram into SPEM after injury. |
| first_indexed | 2024-03-12T23:17:43Z |
| format | Article |
| id | doaj.art-cabec06a0a304c2999d88643e63e8b04 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-03-12T23:17:43Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-cabec06a0a304c2999d88643e63e8b042023-07-17T04:07:43ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2023-01-01163325339SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced MetaplasiaSummarySpencer G. Willet0Nattapon Thanintorn1Helen McNeill2Sung-Ho Huh3David M. Ornitz4Won Jae Huh5Stella G. Hoft6Richard J. DiPaolo7Jason C. Mills8Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri; Correspondence Address correspondence to: Spencer G. Willet, PhD, Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri.Department of Developmental Biology, Washington University School of Medicine, St. Louis, MissouriDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, MissouriDepartment of Otolaryngology–Head and Neck Surgery, University of Mississippi Medical Center, Jackson, MississippiDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, MissouriDepartment of Pathology, Yale School of Medicine, New Haven, ConnecticutDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MissouriDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MissouriSection of Gastroenterology, Department of Medicine, Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas; Jason C. Mills, MD, PhD, Section of Gastroenterology, Department of Medicine, Pathology and Immunology, Baylor College of Medicine, Houston, Texas.Background & Aims: Acute and chronic gastric injury induces alterations in differentiation within the corpus of the stomach called pyloric metaplasia. Pyloric metaplasia is characterized by the death of parietal cells and reprogramming of mitotically quiescent zymogenic chief cells into proliferative, mucin-rich spasmolytic polypeptide–expressing metaplasia (SPEM) cells. Overall, pyloric metaplastic units show increased proliferation and specific expansion of mucous lineages, both by proliferation of normal mucous neck cells and recruitment of SPEM cells. Here, we identify Sox9 as a potential gene of interest in the regulation of mucous neck and SPEM cell identity in the stomach. Methods: We used immunostaining and electron microscopy to characterize the expression pattern of SRY-box transcription factor 9 (SOX9) during murine gastric development, homeostasis, and injury in homeostasis, after genetic deletion of Sox9 and after targeted genetic misexpression of Sox9 in the gastric epithelium and chief cells. Results: SOX9 is expressed in all early gastric progenitors and strongly expressed in mature mucous neck cells with minor expression in the other principal gastric lineages during adult homeostasis. After injury, strong SOX9 expression was induced in the neck and base of corpus units in SPEM cells. Adult corpus units derived from Sox9-deficient gastric progenitors lacked normal mucous neck cells. Misexpression of Sox9 during postnatal development and adult homeostasis expanded mucous gene expression throughout corpus units including within the chief cell zone in the base. Sox9 deletion specifically in chief cells blunts their reprogramming into SPEM. Conclusions: Sox9 is a master regulator of mucous neck cell differentiation during gastric development. Sox9 also is required for chief cells to fully reprogram into SPEM after injury.http://www.sciencedirect.com/science/article/pii/S2352345X23001066StomachDevelopmentMetaplasiaPaligenosis |
| spellingShingle | Spencer G. Willet Nattapon Thanintorn Helen McNeill Sung-Ho Huh David M. Ornitz Won Jae Huh Stella G. Hoft Richard J. DiPaolo Jason C. Mills SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced MetaplasiaSummary Cellular and Molecular Gastroenterology and Hepatology Stomach Development Metaplasia Paligenosis |
| title | SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced MetaplasiaSummary |
| title_full | SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced MetaplasiaSummary |
| title_fullStr | SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced MetaplasiaSummary |
| title_full_unstemmed | SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced MetaplasiaSummary |
| title_short | SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced MetaplasiaSummary |
| title_sort | sox9 governs gastric mucous neck cell identity and is required for injury induced metaplasiasummary |
| topic | Stomach Development Metaplasia Paligenosis |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X23001066 |
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