[PDF][PDF] Intercellular coupling of the cell cycle and circadian clock in adult stem cell culture

T Matsu-Ura, A Dovzhenok, E Aihara, J Rood, H Le… - Molecular cell, 2016 - cell.com
T Matsu-Ura, A Dovzhenok, E Aihara, J Rood, H Le, Y Ren, AE Rosselot, T Zhang, C Lee
Molecular cell, 2016cell.com
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 …
Summary
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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