Mechanical Tension Promotes Formation of Gastrulation-like Nodes and Patterns Mesoderm Specification in Human Embryonic Stem Cells.
Dev Cell
; 55(6): 679-694.e11, 2020 12 21.
Article
in En
| MEDLINE
| ID: mdl-33207224
ABSTRACT
Embryogenesis is directed by morphogens that induce differentiation within a defined tissue geometry. Tissue organization is mediated by cell-cell and cell-extracellular matrix (ECM) adhesions and is modulated by cell tension and tissue-level forces. Whether cell tension regulates development by modifying morphogen signaling is less clear. Human embryonic stem cells (hESCs) exhibit an intrinsic capacity for self-organization, which motivates their use as a tractable model of early human embryogenesis. We engineered patterned substrates that recapitulate the biophysical properties of the early embryo and mediate the self-organization of "gastrulation-like" nodes in cultured hESCs. Tissue geometries that generated local nodes of high cell-adhesion tension directed the spatial patterning of the BMP4-dependent "gastrulation-like" phenotype by enhancing phosphorylation and junctional release of ß-catenin to promote Wnt signaling and mesoderm specification. Furthermore, direct force application via mechanical stretching promoted BMP-dependent mesoderm specification, confirming that tissue-level forces can directly regulate cell fate specification in early human development.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stress, Mechanical
/
Cell Differentiation
/
Gastrulation
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Human Embryonic Stem Cells
/
Mesoderm
Limits:
Animals
/
Humans
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
United States