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Preferred mitotic orientation in pattern formation by vascular mesenchymal cells.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2012 Dec 15; Vol. 303 (12), pp. H1411-7. Date of Electronic Publication: 2012 Oct 12. - Publication Year :
- 2012
-
Abstract
- Cellular self-organization is essential to physiological tissue and organ development. We previously observed that vascular mesenchymal cells, a multipotent subpopulation of aortic smooth muscle cells, self-organize into macroscopic, periodic patterns in culture. The patterns are produced by cells gathering into raised aggregates in the shape of nodules or ridges. To determine whether these patterns are accounted for by an oriented pattern of cell divisions or postmitotic relocation of cells, we acquired time-lapse, videomicrographic phase-contrast, and fluorescence images during self-organization. Cell division events were analyzed for orientation of daughter cells in mitoses during separation and their angle relative to local cell alignment, and frequency distribution of the mitotic angles was analyzed by both histographic and bin-free statistical methods. Results showed a statistically significant preferential orientation of daughter cells along the axis of local cell alignment as early as day 8, just before aggregate formation. This alignment of mitotic axes was also statistically significant at the time of aggregate development (day 11) and after aggregate formation was complete (day 15). Treatment with the nonmuscle myosin II inhibitor, blebbistatin, attenuated alignment of mitotic orientation, whereas Rho kinase inhibition eliminated local cell alignment, suggesting a role for stress fiber orientation in this self-organization. Inhibition of cell division using mitomycin C reduced the macroscopic pattern formation. Time-lapse monitoring of individual cells expressing green fluorescent protein showed postmitotic movement of cells into neighboring aggregates. These findings suggest that polarization of mitoses and postmitotic migration of cells both contribute to self-organization into periodic, macroscopic patterns in vascular stem cells.
- Subjects :
- Animals
Aorta cytology
Cattle
Cells, Cultured
Enzyme Inhibitors pharmacology
Heterocyclic Compounds, 4 or More Rings pharmacology
Mesenchymal Stem Cells drug effects
Microscopy, Video
Mitomycin pharmacology
Models, Animal
Muscle, Smooth, Vascular drug effects
Time-Lapse Imaging
rho-Associated Kinases antagonists & inhibitors
rho-Associated Kinases drug effects
Cell Division drug effects
Cell Polarity drug effects
Mesenchymal Stem Cells cytology
Mitosis drug effects
Muscle, Smooth, Vascular cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 303
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 23064835
- Full Text :
- https://doi.org/10.1152/ajpheart.00625.2012