title: The circadian clock gates the intestinal stem cell regenerative state.
abstract: The intestine has evolved under constant environmental stresses, because an animal may ingest harmful pathogens or chemicals at any time during its lifespan. Following damage, intestinal stem cells (ISCs) regenerate the intestine by proliferating to replace dying cells. ISCs from diverse animals are remarkably similar, and the Wnt, Notch, and Hippo signaling pathways, important regulators of mammalian ISCs, are conserved from flies to humans. Unexpectedly, we identified the transcription factor period, a component of the circadian clock, to be critical for regeneration, which itself follows a circadian rhythm. We discovered hundreds of transcripts that are regulated by the clock during intestinal regeneration, including components of stress response and regeneration pathways. Disruption of clock components leads to arrhythmic ISC divisions, revealing their underappreciated role in the healing process.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. pkarpowicz@genetics.med.harvard.edu
authors.forename: Phillip
authors.initials: P
authors.lastname: Karpowicz
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: John B
authors.initials: JB
authors.lastname: Hogenesch
authors.forename: Patrick
authors.initials: P
authors.lastname: Emery
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000818:Animals; D057906:Circadian Clocks; D002940:Circadian Rhythm; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D007399:Interphase; D007422:Intestines / Q000166:cytology / Q000502:physiology; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D056950:Period Circadian Proteins