Human bone marrow mesenchymal stem cells regulate biased DNA segregation in response to cell adhesion asymmetry.

Delphine Freida (1, 2) , Severine Lecourt (2) , Audrey Cras (2) , Valérie Vanneaux (2) , Gaelle Letort (3) , Xavier Gidrol (1) , Laurent Guyon (1) , Jerome Larghero (2) , Manuel Thery (3, 4)

1 BGE - UMR S1038 - Laboratoire de Biologie à Grande Échelle
2 Unité de Thérapie Cellulaire
3 LPCV - Laboratoire de physiologie cellulaire végétale
4 BIG - Institut de Biosciences et de Biotechnologies de Grenoble (ex-IRTSV)

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.

Mots clés: human; mesenchymal stem cells; mitosis; cell adhesion; spatial distribution; micropatterns

Domaines: Biologie cellulaire

Delphine Freida, Severine Lecourt, Audrey Cras, Valérie Vanneaux, Gaelle Letort, et al.. Human bone marrow mesenchymal stem cells regulate biased DNA segregation in response to cell adhesion asymmetry.. Cell Reports, 2013, 5 (3), pp.601-10. ⟨10.1016/j.celrep.2013.09.019⟩. ⟨hal-00942921⟩