Cell adhesion geometry regulates non-random DNA segregation and asymmetric cell fates in mouse skeletal muscle stem cells.
Cells of several metazoan species have been shown to non-randomly segregate their DNA such that older template DNA strands segregate to one daughter cell. The mechanisms that regulate this asymmetry remain undefined. Determinants of cell fate are polarized during mitosis and partitioned asymmetrically as the spindle pole orients during cell division. Chromatids align along the pole axis; therefore, it is unclear whether extrinsic cues that determine spindle pole position also promote non-random DNA segregation. To mimic the asymmetric divisions seen in the mouse skeletal stem cell niche, we used micropatterns coated with extracellular matrix in asymmetric and symmetric motifs. We show that the frequency of non-random DNA segregation and transcription factor asymmetry correlates with the shape of the motif and that these events can be uncoupled. Furthermore, regulation of DNA segregation by cell adhesion occurs within a defined time interval. Thus, cell adhesion cues have a major impact on determining both DNA segregation patterns and cell fates.
Institut Pasteur, Stem Cells & Development, Department of Developmental & Stem Cell Biology, CNRS URA 2578, 25 rue du Dr. Roux, Paris F-75015, France; Sorbonne Universités, UPMC, University of Paris 06, IFD-ED 515, 4 Place Jussieu, Paris 75252, France.
Siham
S
Yennek
Institut de Recherche en Technologie et Science pour le Vivant, UMR5168, CEA/UJF/INRA/CNRS, 17 rue des Martyrs, Grenoble 38054, France; CYTOO SA, 7 Parvis Louis Néel, BP50, Grenoble 38040, France; Hôpital Saint Louis, Institut Universitaire d'Hematologie, U1160, INSERM/AP-HP/Université Paris Diderot, 1 Avenue Claude Vellefaux, Paris 75010, France.
Mithila
M
Burute
Institut de Recherche en Technologie et Science pour le Vivant, UMR5168, CEA/UJF/INRA/CNRS, 17 rue des Martyrs, Grenoble 38054, France; Hôpital Saint Louis, Institut Universitaire d'Hematologie, U1160, INSERM/AP-HP/Université Paris Diderot, 1 Avenue Claude Vellefaux, Paris 75010, France.
Manuel
M
Théry
Institut Pasteur, Stem Cells & Development, Department of Developmental & Stem Cell Biology, CNRS URA 2578, 25 rue du Dr. Roux, Paris F-75015, France. Electronic address: shahragim.tajbakhsh@pasteur.fr.
Shahragim
S
Tajbakhsh
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D004247:DNA