Journal article

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The circadian molecular clock creates epidermal stem cell heterogeneity

  • Janich, Peggy Center for Genomic Regulation and UPF, Barcelona, Spain
  • Pascual, Gloria Center for Genomic Regulation and UPF, Barcelona, Spain
  • Merlos-Suárez, Anna Institute for Research in Biomedicine, Barcelona, Spain
  • Batlle, Eduard Institute for Research in Biomedicine, Barcelona, Spain - Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
  • Ripperger, Jürgen A. University of Fribourg, Switzerland
  • Albrecht, Urs University of Fribourg, Switzerland
  • Obrietan, Karl Ohio State University, Columbus, USA
  • Croce, Luciano Di Center for Genomic Regulation and UPF, Barcelona, Spain - Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
  • Benitah, Salvador Aznar Center for Genomic Regulation and UPF, Barcelona, Spain - Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
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    09.11.2011
Published in:
  • Nature. - 2011
English Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/302091
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