TY - JOUR TI - Mother cells control daughter cell proliferation in intestinal organoids to minimize proliferation fluctuations AU - Huelsz-Prince, Guizela AU - Kok, Rutger Nico Ulbe AU - Goos, Yvonne AU - Bruens, Lotte AU - Zheng, Xuan AU - Ellenbroek, Saskia AU - Van Rheenen, Jacco AU - Tans, Sander AU - van Zon, Jeroen S A2 - Rulands, Steffen A2 - Stainier, Didier YR A2 - Greulich, Philip VL - 11 PY - 2022 DA - 2022/11/29 SP - e80682 C1 - eLife 2022;11:e80682 DO - 10.7554/eLife.80682 UR - https://doi.org/10.7554/eLife.80682 AB - 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. KW - stem cell dynamics KW - intestinal epithelium KW - fluctuations KW - cell proliferation KW - cell lineage KW - time-lapse microscopy JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -