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Cytoskeletal tension regulates mesodermal spatial organization and subsequent vascular fate.


ABSTRACT: Morphogenesis during human development relies on the interplay between physiochemical cues that are mediated in part by cellular density and cytoskeletal tension. Here, we interrogated these factors on vascular lineage specification during human-induced pluripotent stem-cell (hiPSC) fate decision. We found that independent of chemical cues, spatially presented physical cues induce the self-organization of Brachyury-positive mesodermal cells, in a RhoA/Rho-associated kinase (ROCK)-dependent manner. Using unbiased support vector machine (SVM) learning, we found that density alone is sufficient to predict mesodermal fate. Furthermore, the long-withstanding presentation of spatial confinement during hiPSC differentiation led to an organized vascular tissue, reminiscent of native blood vessels, a process dependent on cell density as found by SVM analysis. Collectively, these results show how tension and density relate to vascular identity mirroring early morphogenesis. We propose that such a system can be applied to study other aspects of the stem-cell niche and its role in embryonic patterning.

SUBMITTER: Smith Q 

PROVIDER: S-EPMC6094121 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Cytoskeletal tension regulates mesodermal spatial organization and subsequent vascular fate.

Smith Quinton Q   Rochman Nash N   Carmo Ana Maria AM   Vig Dhruv D   Chan Xin Yi XY   Sun Sean S   Gerecht Sharon S  

Proceedings of the National Academy of Sciences of the United States of America 20180723 32


Morphogenesis during human development relies on the interplay between physiochemical cues that are mediated in part by cellular density and cytoskeletal tension. Here, we interrogated these factors on vascular lineage specification during human-induced pluripotent stem-cell (hiPSC) fate decision. We found that independent of chemical cues, spatially presented physical cues induce the self-organization of Brachyury-positive mesodermal cells, in a RhoA/Rho-associated kinase (ROCK)-dependent manne  ...[more]

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