期刊
GASTROENTEROLOGY
卷 154, 期 4, 页码 839-+出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2017.11.278
关键词
Development; Differentiation; Exocrine Cell; Cancer
资金
- National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases [DK094989, DK105129, DK110406]
- Alvin J. Siteman Cancer Center/Barnes Jewish Hospital Foundation Cancer Frontier Fund
- NIH National Cancer Institute [P30 CA091842]
- Barnard Trust
- NIH [5T32GM007067-43]
- National Institute of General Medical Sciences Cell and Molecular Biology training grant [GM007067]
- Philip and Sima Needleman Student Fellowship in Regenerative Medicine to Joseph Burclaff
- National Cancer Institute training grant [CA00954731]
- Digestive Disease Research Core Centers and Advanced Imaging and Tissue Analysis Core [P30DK052574]
- Alafi Neuroimaging Laboratory
- Hope Center for Neurological Disorders
- NIH Shared Instrumentation Grant [S10 RR0227552]
- NATIONAL CANCER INSTITUTE [P30CA091842] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK052574, R01DK094989, R01DK079798, R01DK105129, R01DK110406] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007067] Funding Source: NIH RePORTER
Spasmolytic polypeptide-expressing metaplasia (SPEM) develops in patients with chronic atrophic gastritis due to infection with Helicobacter pylori; it might be a precursor to intestinal metaplasia and gastric adenocarcinoma. Lineage tracing experiments of the gastric corpus in mice have not established whether SPEM derives from proliferating stem cells or differentiated, post-mitotic zymogenic chief cells in the gland base. We investigated whether differentiated cells can give rise to SPEM using a non-genetic approach in mice. Mice were given intraperitoneal injections of 5-fluorouracil, which blocked gastric cell proliferation, plus tamoxifen to induce SPEM. Based on analyses of molecular and histologic markers, we found SPEM developed even in the absence of cell proliferation. SPEM therefore did not arise from stem cells. In histologic analyses of gastric resection specimens from 10 patients with adenocarcinoma, we found normal zymogenic chief cells that were transitioning into SPEM cells only in gland bases, rather than the proliferative stem cell zone. Our findings indicate that SPEM can arise by direct reprogramming of existing cells-mainly of chief cells.
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