Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors

Kshitiz, Maimon E. Hubbi, Eun Hyun Ahn, John Downey, Junaid Afzal, Deok Ho Kim, Sergio Rey, Connie Chang, Arnab Kundu, Gregg L Semenza, Roselle M. Abraham, Andre Levchenko

Research output: Contribution to journalArticle

Abstract

Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood.We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase- activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.

Original languageEnglish (US)
Article numberra41
JournalScience Signaling
Volume5
Issue number227
DOIs
StatePublished - Jun 5 2012

Fingerprint

Morphogenesis
Rigidity
rhoA GTP-Binding Protein
Tissue
Guanosine
Networks (circuits)
Cell Communication
Regeneration
Cell Differentiation
Myocardium
Stem Cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Kshitiz, Hubbi, M. E., Ahn, E. H., Downey, J., Afzal, J., Kim, D. H., ... Levchenko, A. (2012). Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors. Science Signaling, 5(227), [ra41]. https://doi.org/10.1126/scisignal.2003002

Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors. / Kshitiz; Hubbi, Maimon E.; Ahn, Eun Hyun; Downey, John; Afzal, Junaid; Kim, Deok Ho; Rey, Sergio; Chang, Connie; Kundu, Arnab; Semenza, Gregg L; Abraham, Roselle M.; Levchenko, Andre.

In: Science Signaling, Vol. 5, No. 227, ra41, 05.06.2012.

Research output: Contribution to journalArticle

Kshitiz, Hubbi, ME, Ahn, EH, Downey, J, Afzal, J, Kim, DH, Rey, S, Chang, C, Kundu, A, Semenza, GL, Abraham, RM & Levchenko, A 2012, 'Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors', Science Signaling, vol. 5, no. 227, ra41. https://doi.org/10.1126/scisignal.2003002
Kshitiz ; Hubbi, Maimon E. ; Ahn, Eun Hyun ; Downey, John ; Afzal, Junaid ; Kim, Deok Ho ; Rey, Sergio ; Chang, Connie ; Kundu, Arnab ; Semenza, Gregg L ; Abraham, Roselle M. ; Levchenko, Andre. / Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors. In: Science Signaling. 2012 ; Vol. 5, No. 227.
@article{ab725e05d4bc4247bd44406046873506,
title = "Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors",
abstract = "Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood.We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase- activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.",
author = "Kshitiz and Hubbi, {Maimon E.} and Ahn, {Eun Hyun} and John Downey and Junaid Afzal and Kim, {Deok Ho} and Sergio Rey and Connie Chang and Arnab Kundu and Semenza, {Gregg L} and Abraham, {Roselle M.} and Andre Levchenko",
year = "2012",
month = "6",
day = "5",
doi = "10.1126/scisignal.2003002",
language = "English (US)",
volume = "5",
journal = "Science Signaling",
issn = "1937-9145",
publisher = "American Association for the Advancement of Science",
number = "227",

}

TY - JOUR

T1 - Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors

AU - Kshitiz,

AU - Hubbi, Maimon E.

AU - Ahn, Eun Hyun

AU - Downey, John

AU - Afzal, Junaid

AU - Kim, Deok Ho

AU - Rey, Sergio

AU - Chang, Connie

AU - Kundu, Arnab

AU - Semenza, Gregg L

AU - Abraham, Roselle M.

AU - Levchenko, Andre

PY - 2012/6/5

Y1 - 2012/6/5

N2 - Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood.We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase- activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.

AB - Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood.We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase- activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.

UR - http://www.scopus.com/inward/record.url?scp=84862128771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862128771&partnerID=8YFLogxK

U2 - 10.1126/scisignal.2003002

DO - 10.1126/scisignal.2003002

M3 - Article

C2 - 22669846

AN - SCOPUS:84862128771

VL - 5

JO - Science Signaling

JF - Science Signaling

SN - 1937-9145

IS - 227

M1 - ra41

ER -