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Compliant substratum guides endothelial commitment from human pluripotent stem cells.

Publication ,  Journal Article
Smith, Q; Chan, XY; Carmo, AM; Trempel, M; Saunders, M; Gerecht, S
Published in: Science advances
May 2017

The role of mechanical regulation in driving human induced pluripotent stem cell (hiPSC) differentiation has been minimally explored. Although endothelial cell (EC) fate from hiPSCs has been demonstrated using small molecules to drive mesoderm induction, the effects of substrate stiffness with regard to EC differentiation efficiency have yet to be elucidated. We hypothesized that substrate compliance can modulate mesoderm differentiation kinetics from hiPSCs and affect downstream EC commitment. To this end, we used polydimethylsiloxane (PDMS)-a transparent, biocompatible elastomeric material-as a substrate to study EC commitment of hiPSCs using a stepwise differentiation scheme. Using physiologically stiff (1.7 MPa) and soft (3 kPa) PDMS substrates, compared to polystyrene plates (3 GPa), we demonstrate that mechanical priming during mesoderm induction activates the Yes-associated protein and drives Wnt/β-catenin signaling. When mesoderm differentiation was induced on compliant PDMS substrates in both serum and serum-free E6 medium, mesodermal genetic signatures (T, KDR, MESP-1, GATA-2, and SNAIL-1) were enhanced. Furthermore, examination of EC fate following stiffness priming revealed that compliant substrates robustly improve EC commitment through VECad, CD31, vWF, and eNOS marker expression. Overall, we show that substrate compliance guides EC fate by enhancing mesoderm induction through Wnt activation without the addition of small molecules. These findings are the first to show that the mechanical context of the differentiation niche can be as potent as chemical cues in driving EC identity from hiPSCs.

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Published In

Science advances

DOI

EISSN

2375-2548

ISSN

2375-2548

Publication Date

May 2017

Volume

3

Issue

5

Start / End Page

e1602883

Related Subject Headings

  • Stress, Mechanical
  • Induced Pluripotent Stem Cells
  • Humans
  • Gene Expression Regulation
  • Endothelial Cells
  • Elastomers
  • Cells, Cultured
  • Cell Differentiation
  • Cell Culture Techniques
  • Biocompatible Materials
 

Citation

APA
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ICMJE
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Smith, Q., Chan, X. Y., Carmo, A. M., Trempel, M., Saunders, M., & Gerecht, S. (2017). Compliant substratum guides endothelial commitment from human pluripotent stem cells. Science Advances, 3(5), e1602883. https://doi.org/10.1126/sciadv.1602883
Smith, Quinton, Xin Yi Chan, Ana Maria Carmo, Michelle Trempel, Michael Saunders, and Sharon Gerecht. “Compliant substratum guides endothelial commitment from human pluripotent stem cells.Science Advances 3, no. 5 (May 2017): e1602883. https://doi.org/10.1126/sciadv.1602883.
Smith Q, Chan XY, Carmo AM, Trempel M, Saunders M, Gerecht S. Compliant substratum guides endothelial commitment from human pluripotent stem cells. Science advances. 2017 May;3(5):e1602883.
Smith, Quinton, et al. “Compliant substratum guides endothelial commitment from human pluripotent stem cells.Science Advances, vol. 3, no. 5, May 2017, p. e1602883. Epmc, doi:10.1126/sciadv.1602883.
Smith Q, Chan XY, Carmo AM, Trempel M, Saunders M, Gerecht S. Compliant substratum guides endothelial commitment from human pluripotent stem cells. Science advances. 2017 May;3(5):e1602883.

Published In

Science advances

DOI

EISSN

2375-2548

ISSN

2375-2548

Publication Date

May 2017

Volume

3

Issue

5

Start / End Page

e1602883

Related Subject Headings

  • Stress, Mechanical
  • Induced Pluripotent Stem Cells
  • Humans
  • Gene Expression Regulation
  • Endothelial Cells
  • Elastomers
  • Cells, Cultured
  • Cell Differentiation
  • Cell Culture Techniques
  • Biocompatible Materials