title: Human bone marrow mesenchymal stem cells regulate biased DNA segregation in response to cell adhesion asymmetry.
abstract: Biased DNA segregation is a mitotic event in which the chromatids carrying the original template DNA strands and those carrying the template copies are not segregated randomly into the two daughter cells. Biased segregation has been observed in several cell types, but not in human mesenchymal stem cells (hMSCs), and the factors affecting this bias have yet to be identified. Here, we have investigated cell adhesion geometries as a potential parameter by plating hMSCs from healthy donors on fibronectin-coated micropatterns. On symmetric micropatterns, the segregation of sister chromatids to the daughter cells appeared random. In contrast, on asymmetric micropatterns, the segregation was biased. This sensitivity to asymmetric extracellular cues was reproducible in cells from all donors but was not observed in human skin-derived fibroblasts or in a fibroblastic cell line used as controls. We conclude that the asymmetry of cell adhesion is a major factor in the regulation of biased DNA segregation in hMSCs.
authors.affiliation: CEA, Institut de Recherches en Technologies et Sciences pour le Vivant, 17 Rue des Martyrs, 38054 Grenoble, France; University Grenoble-Alpes, F-38041 Grenoble, France; INSERM, U1038, F-38054 Grenoble, France; AP-HP, Hôpital Saint Louis, Unité de Thérapie Cellulaire et Centre d'Investigation Clinique en Biothérapies (CBT501), F-75475 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, F-75475 Paris, France; INSERM, UMRS940, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, F-75475 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Freida
authors.forename: Severine
authors.initials: S
authors.lastname: Lecourt
authors.forename: Audrey
authors.initials: A
authors.lastname: Cras
authors.forename: Valérie
authors.initials: V
authors.lastname: Vanneaux
authors.forename: Gaelle
authors.initials: G
authors.lastname: Letort
authors.forename: Xavier
authors.initials: X
authors.lastname: Gidrol
authors.forename: Laurent
authors.initials: L
authors.lastname: Guyon
authors.forename: Jerome
authors.initials: J
authors.lastname: Larghero
authors.forename: Manuel
authors.initials: M
authors.lastname: Thery
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002842:Chromatids / Q000235:genetics; D020090:Chromosome Segregation; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D008677:Metaphase / Q000235:genetics
chemical_list: D005353:Fibronectins; D004247:DNA