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

Matsuura, Toru; Dovzhenok, Andrey; Aihara, Eitaro; Rood, Jill K; Le, Hung; Ren, Yan; Rosselot, Andrew E.; Zhang, Tongli; Lee, Choogon; Obrietan, Karl; Montrose, Marshall H.; Lim, Sookkyung; Moore, Sean R.; Hong, Christian I.

doi:10.1016/j.molcel.2016.10.015

Cited by 103 publications

(115 citation statements)

References 49 publications

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“…The loss of BMAL1 produced no obvious differences in intestinal crypt or villus morphology; however, a slight but significant decline in the number of crypts was noted (Figure 3 A ). This result is consistent with recent findings that the PER1/PER2 double mutant also has a slight decrease in crypt number 28 . The BMAL1 -related difference in baseline crypt number may explain the overall reduction in the number of crypts following irradiation (Figure 2 A ).…”

Section: Resultssupporting

confidence: 93%

“…Although these phenotypes seem to be generally compensated during maintenance in vivo (Figure 3) and in vitro (Figure 5 E ), the circadian clock may play a role in epithelial Wnt signaling in certain physiological contexts. While this study was under revision, it was reported that Wnt signaling is regulated by the clock in intestinal organoids, caused by the expression of WNT3A by Paneth cells 28 . Circadian control of intestinal signaling pathways may be an important mechanism linking tissue homeostasis with general physiology.…”

Section: Discussionmentioning

confidence: 86%

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The Circadian Clock Gene BMAL1 Coordinates Intestinal Regeneration

Stokes

Cooke

Chang

et al. 2017

Cellular and Molecular Gastroenterology and Hepatology

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Background & AimsThe gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied.MethodsWe tested the timing of regeneration in the mouse intestine during the gastrointestinal syndrome. The role of the circadian clock was tested genetically using the BMAL1 loss of function mouse mutant in vivo, and in vitro using intestinal organoid culture.ResultsThe proliferation of the intestinal epithelium follows a 24-hour rhythm during the gastrointestinal syndrome. The circadian clock runs in the intestinal epithelium during this pathologic state, and the loss of the core clock gene, BMAL1, disrupts both the circadian clock and rhythmic proliferation. Circadian activity in the intestine involves a rhythmic production of inflammatory cytokines and subsequent rhythmic activation of the JNK stress response pathway.ConclusionsOur results show that a circadian rhythm in inflammation and regeneration occurs during the gastrointestinal syndrome. The study and treatment of radiation-induced illnesses, and other gastrointestinal illnesses, should consider 24-hour timing in physiology and pathology.

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Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 86%

The Circadian Clock Gene BMAL1 Coordinates Intestinal Regeneration

Stokes

Cooke

Chang

et al. 2017

Cellular and Molecular Gastroenterology and Hepatology

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“…The cell cycle consists of a series of phases, including DNA replication, various checkpoints and cell division, that allow cell proliferation. Previous studies in cyanobacteria, fungi, plant, zebrafish, and mammals have showed that circadian clocks influence the cell cycle to gate the timing of different phases of DNA synthesis, checkpoints, and cytokinesis (Dekens et al, 2003; Dong et al, 2010; Feillet et al, 2014; Hirayama et al, 2005; Hong et al, 2014; Kowalska et al, 2013; Laranjeiro et al, 2013; Masri et al, 2013; Matsu-Ura et al, 2016; Matsuo et al, 2003; Mori et al, 1996; Nagoshi et al, 2004). …”

Section: Introductionmentioning

confidence: 99%

DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition

et al. 2017

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SUMMARY Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in circadian mechanism.

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“…Although the physiological relevance of this finding is still controversial, computational models suggest that the circadian rhythm synchronizes this rhythmic cell cycle entry. [50]…”

Section: Computational Modeling Of Intestinal Organoid Systemsmentioning

confidence: 99%

Bioengineering for intestinal organoid cultures

Kim

Spence

Takayama

2017

Current Opinion in Biotechnology

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Recent advances allow access to human cell-based intestinal organoids that recreate human physiology to levels not possible with conventional 2D cell cultures. Despite their huge potential, there are many challenges that remain. This review will cover recent bioengineering approaches to improve organoid maturation, scale up, reproducibility and analysis. The first section covers the advances in engineering the culture environment, followed by the section on tools for micro-manipulation and analysis of organoids. The last section reviews the computational models developed to guide the use of engineered materials and tools, and to interpret observed results as well. The ability to use organoids for discovery research, and the need to both exert exquisite experimental control and obtain quantitative measurements from organoid models means that the field is ripe for collaborative efforts between biologists, engineers, clinicians and industry.

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

Cited by 103 publications

References 49 publications

The Circadian Clock Gene BMAL1 Coordinates Intestinal Regeneration

The Circadian Clock Gene BMAL1 Coordinates Intestinal Regeneration

DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition

Bioengineering for intestinal organoid cultures

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