RRC ID 47633
Author Matsu-Ura T, Dovzhenok A, Aihara E, Rood J, Le H, Ren Y, Rosselot AE, Zhang T, Lee C, Obrietan K, Montrose MH, Lim S, Moore SR, Hong CI.
Title Intercellular Coupling of the Cell Cycle and Circadian Clock in Adult Stem Cell Culture.
Journal Mol. Cell
Abstract 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.
Volume 64(5)
Pages 900-912
Published 2016-12-1
DOI 10.1016/j.molcel.2016.10.015
PII S1097-2765(16)30638-4
PMID 27867006
PMC PMC5423461
MeSH Adult Stem Cells / physiology Animals Cell Cycle / physiology* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Circadian Clocks / physiology* Circadian Rhythm Intestinal Mucosa / physiology* Jejunum / metabolism Mice Nuclear Proteins / genetics Nuclear Proteins / metabolism Organoids Period Circadian Proteins / genetics Period Circadian Proteins / metabolism Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism Tissue Culture Techniques Wnt Signaling Pathway / physiology*
IF 14.248
Times Cited 4
DNA material CSII-EF-MCS (RDB04378)