The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1
| العنوان: | The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1 |
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| المؤلفون: | Christopher C.M. Chen, Stephen F. Konieczny, Thaddeus S. Stappenbeck, Jason M. Doherty, Jason C. Mills, Victoria G. Ramsey |
| المصدر: | Oncological Sciences Center Publications |
| بيانات النشر: | The Company of Biologists, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Cell, Biology, Cytoplasmic Granules, Models, Biological, Mice, Parietal Cells, Gastric, Zymogen, Basic Helix-Loop-Helix Transcription Factors, medicine, Animals, Cell Lineage, Progenitor cell, Molecular Biology, Transcription factor, Laser capture microdissection, Mice, Knockout, Gene Expression Profiling, Regeneration (biology), Stomach, Epithelial Cells, Immunohistochemistry, Mucus, Cell biology, Gastric chief cell, medicine.anatomical_structure, Gastric Mucosa, Bhlhb8, mucous neck cell, laser-capture microdissection, microarray, mouse, TRANSCRIPTION FACTOR MIST1, SEROUS EXOCRINE CELLS, MOUSE STOMACH, GASTROINTESTINAL-TRACT, PARIETAL-CELLS, NECK CELLS, CORPUS, DYNAMICS, CANCER, MICE, Immunology, Developmental Biology |
| الوصف: | Continuous regeneration of digestive enzyme (zymogen)-secreting chief cells is a normal aspect of stomach function that is disrupted in precancerous lesions (e.g. metaplasias, chronic atrophy). The cellular and genetic pathways that underlie zymogenic cell (ZC) differentiation are poorly understood. Here,we describe a gene expression analysis of laser capture microdissection purified gastric cell populations that identified the bHLH transcription factor Mist1 as a potential ZC regulatory factor. Our molecular and ultrastructural analysis of proliferation, migration and differentiation of the gastric unit in Mist1-/- and control mice supports a model whereby wild-type ZC progenitors arise as neck cells in the proliferative (isthmal) zone of the gastric unit and become transitional cells(TCs) with molecular and ultrastructural characteristics of both enzyme-secreting ZCs and mucus-secreting neck cells as they migrate to the neck-base zone interface. Thereafter, they rapidly differentiate into mature ZCs as they enter the base. By contrast, Mist1-/- neck cells differentiate normally, but ZCs in the mature, basal portion of the gastric unit uniformly exhibit multiple apical cytoplasmic structural abnormalities. This defect in terminal ZC differentiation is also associated with markedly increased abundance of TCs, especially in late-stage TCs that predominantly have features of immature ZCs. Thus, we present an in vivo system for analysis of ZC differentiation, present molecular evidence that ZCs differentiate from neck cell progenitors and identify Mist1 as the first gene with a role in this clinically important process. |
| وصف الملف: | application/pdf |
| تدمد: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.02700 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77406519230fa24ac407ad9fbaa0c855 https://doi.org/10.1242/dev.02700 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....77406519230fa24ac407ad9fbaa0c855 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779129 09501991 |
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| DOI: | 10.1242/dev.02700 |