期刊
ELIFE
卷 11, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.80682
关键词
stem cell dynamics; intestinal epithelium; fluctuations; cell proliferation; cell lineage; time-lapse microscopy; Mouse
类别
资金
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- [680-47-529]
- [737.016.009]
During the renewal of the intestine, the proliferative behavior of cells in the crypts exhibits a high degree of symmetry between sister cells, which minimizes fluctuations in cell number. This behavior is controlled through the mother cell's lineage and provides a concrete mechanism to balance proliferation and differentiation.
During renewal of the intestine, cells are continuously generated by proliferation. Proliferation and differentiation must be tightly balanced, as any bias toward proliferation results in uncontrolled exponential growth. Yet, the inherently stochastic nature of cells raises the question how such fluctuations are limited. We used time-lapse microscopy to track all cells in crypts of growing mouse intestinal organoids for multiple generations, allowing full reconstruction of the underlying lineage dynamics in space and time. Proliferative behavior was highly symmetric between sister cells, with both sisters either jointly ceasing or continuing proliferation. Simulations revealed that such symmetric proliferative behavior minimizes cell number fluctuations, explaining our observation that proliferating cell number remained constant even as crypts increased in size considerably. Proliferative symmetry did not reflect positional symmetry but rather lineage control through the mother cell. Our results indicate a concrete mechanism to balance proliferation and differentiation with minimal fluctuations that may be broadly relevant for other tissues.
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