title: Circadian Clock Genes Modulate Human Bone Marrow Mesenchymal Stem Cell Differentiation, Migration and Cell Cycle.
abstract: Many of the components that regulate the circadian clock have been identified in organisms and humans. The influence of circadian rhythm (CR) on the regulation of stem cells biology began to be evaluated. However, little is known on the role of CR on human mesenchymal stem cell (hMSCs) properties. The objective of this study was to investigate the influence of CR on the differentiation capacities of bone marrow hMSCs, as well as the regulation of cell cycle and migration capabilities. To that, we used both a chemical approach with a GSK-3β specific inhibitor (2'E,3'Z-6-bromoindirubin-3'-oxime, BIO) and a knockdown of CLOCK and PER2, two of the main genes involved in CR regulation. In these experimental conditions, a dramatic inhibition of adipocyte differentiation was observed, while osteoblastic differentiation capacities were not modified. In addition, cell migration was decreased in PER2-/- cells. Lastly, downregulation of circadian clock genes induced a modification of the hMSCs cell cycle phase distribution, which was shown to be related to a change of the cyclin expression profile. Taken together, these data showed that CR plays a role in the regulation of hMSCs differentiation and division, and likely represent key factor in maintaining hMSCs properties.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Cell Therapy Unit, Paris, France.|University Paris Descartes, School of Pharmacy, Paris, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Boucher
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Cell Therapy Unit, Paris, France.|INSERM, CIC de Biothérapies (CBT-501) and UMR1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Vanneaux
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Cell Therapy Unit, Paris, France.|INSERM, CIC de Biothérapies (CBT-501) and UMR1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Domet
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Cell Therapy Unit, Paris, France.|INSERM, CIC de Biothérapies (CBT-501) and UMR1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Parouchev
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Cell Therapy Unit, Paris, France.|INSERM, CIC de Biothérapies (CBT-501) and UMR1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.|University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Larghero
mesh_terms: D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D057906:Circadian Clocks / Q000235:genetics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*
chemical_list: D056926:CLOCK Proteins