Cytoskeletal tension regulates mesodermal spatial organization and subsequent vascular fate.
Proc Natl Acad Sci U S A
; 115(32): 8167-8172, 2018 08 07.
Article
en En
| MEDLINE
| ID: mdl-30038020
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Citoesqueleto
/
Linaje de la Célula
/
Tipificación del Cuerpo
/
Células Madre Pluripotentes Inducidas
/
Mesodermo
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2018
Tipo del documento:
Article