Mother cells control daughter cell proliferation in intestinal organoids to minimize proliferation fluctuations

Guizela Huelsz-Prince, Rutger Nico Ulbe Kok, Yvonne Goos, Lotte Bruens, Xuan Zheng, Saskia Ellenbroek, Jacco Van Rheenen, Sander Tans, Jeroen S. van Zon*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review


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 ques-tion 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 obser-vation 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.

Original languageEnglish
Article numbere80682
Number of pages21
Publication statusPublished - 2022
Externally publishedYes


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