Intercellular Coupling of the Cell Cycle and Circadian Clock in Adult Stem Cell Culture

Research paper by Toru Matsu-ura, Andrey Dovzhenok, Eitaro Aihara, Jill Rood, Hung Le, Yan Ren, Andrew E. Rosselot, Tongli Zhang, Choogon Lee, Karl Obrietan, Marshall H. Montrose, Sookkyung Lim, Sean R. Moore, Christian I. Hong

Indexed on: 19 Nov '16Published on: 17 Nov '16Published in: Molecular Cell


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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