期刊
MOLECULAR CELL
卷 64, 期 5, 页码 900-912出版社
CELL PRESS
DOI: 10.1016/j.molcel.2016.10.015
关键词
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资金
- Department of Interior [D12AP00005]
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [1354612] Funding Source: National Science Foundation
Circadian clock-gated cell division cycles are observed from cyanobacteria to mammals via intracellular molecular connections between these two oscillators. Here we demonstrate WNT-mediated intercellular coupling between the cell cycle and circadian clock in 3D murine intestinal organoids (enteroids). The circadian clock gates a population of cells with heterogeneous cell-cycle times that emerge as 12-hr synchronized cell division cycles. Remarkably, we observe reduced-amplitude oscillations of circadian rhythms in intestinal stem cells and progenitor cells, indicating an intercellular signal arising from differentiated cells governing circadian clock-dependent synchronized cell division cycles. Stochastic simulations and experimental validations reveal Paneth cell-secreted WNT as the key intercellular coupling component linking the circadian clock and cell cycle in enteroids.
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