Laminin 411 mediates endothelial specification via multiple signaling axes that converge on β-catenin

Mikayla L. Hall; Sophie Givens; Natasha Santosh; Michelina Iacovino; Michael Kyba; Brenda M. Ogle

doi:10.1016/j.stemcr.2022.01.005

Laminin 411 mediates endothelial specification via multiple signaling axes that converge on β-catenin

Mikayla L. Hall
, Sophie Givens
, Natasha Santosh
, Michelina Iacovino
, Michael Kyba
, Brenda M. Ogle

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

The extracellular matrix (ECM) provides essential cues to promote endothelial specification during tissue development in vivo; correspondingly, ECM is considered essential for endothelial differentiation outside of the body. However, systematic studies to assess the precise contribution of individual ECM proteins to endothelial differentiation have not been conducted. Further, the multi-component nature of differentiation protocols makes it challenging to study the underlying mechanisms by which the ECM contributes to cell fate. In this study, we determined that Laminin 411 alone increases endothelial differentiation of induced pluripotent stem cells over collagen I or Matrigel. The effect of ECM was shown to be independent of vascular endothelial growth factor (VEGF) binding capacity. We also show that ECM-guided endothelial differentiation is dependent on activation of focal adhesion kinase (FAK), integrin-linked kinase (ILK), Notch, and β-catenin pathways. Our results indicate that ECM contributes to endothelial differentiation through multiple avenues, which converge at the expression of active β-catenin.

Original language	English (US)
Pages (from-to)	569-583
Number of pages	15
Journal	Stem Cell Reports
Volume	17
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2022.01.005
State	Published - Mar 8 2022

Bibliographical note

Funding Information:
We would like to thank the Srivastava lab, University of California, San Francisco, for providing the miPSCs used in this study. We would also like to thank the Zhang Lab at the University of Alabama at Birmingham for providing the cell line hciPSC-MHC-CCND2 (human cardiac fibroblast-derived induced pluripotent stem cells expressing cyclin D2 under the myosin heavy chain promoter) used for all hiPSC experiments. This research was funded by grants from National Institutes of Health R01 HL137204 to B.M.O.; National Institutes of Health R01 AR075413 to M.K.; National Institutes of Health Stem Cell Biology T32 GM113846-09 to M.L.H. Dinnaken Fellowship Funding by PACCS Division, Department of Medicine, University of Minnesota to M.L.H. and National Science Foundation GRFP to S.G.

Publisher Copyright:
© 2022 The Authors

Keywords

beta catenin
cell signaling
differentiation
endothelial cells
extracellular matrix
focal adhesion
laminin
signal transduction
stem cells
vascular

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10.1016/j.stemcr.2022.01.005

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title = "Laminin 411 mediates endothelial specification via multiple signaling axes that converge on β-catenin",

abstract = "The extracellular matrix (ECM) provides essential cues to promote endothelial specification during tissue development in vivo; correspondingly, ECM is considered essential for endothelial differentiation outside of the body. However, systematic studies to assess the precise contribution of individual ECM proteins to endothelial differentiation have not been conducted. Further, the multi-component nature of differentiation protocols makes it challenging to study the underlying mechanisms by which the ECM contributes to cell fate. In this study, we determined that Laminin 411 alone increases endothelial differentiation of induced pluripotent stem cells over collagen I or Matrigel. The effect of ECM was shown to be independent of vascular endothelial growth factor (VEGF) binding capacity. We also show that ECM-guided endothelial differentiation is dependent on activation of focal adhesion kinase (FAK), integrin-linked kinase (ILK), Notch, and β-catenin pathways. Our results indicate that ECM contributes to endothelial differentiation through multiple avenues, which converge at the expression of active β-catenin.",

keywords = "beta catenin, cell signaling, differentiation, endothelial cells, extracellular matrix, focal adhesion, laminin, signal transduction, stem cells, vascular",

author = "Hall, \{Mikayla L.\} and Sophie Givens and Natasha Santosh and Michelina Iacovino and Michael Kyba and Ogle, \{Brenda M.\}",

note = "Funding Information: We would like to thank the Srivastava lab, University of California, San Francisco, for providing the miPSCs used in this study. We would also like to thank the Zhang Lab at the University of Alabama at Birmingham for providing the cell line hciPSC-MHC-CCND2 (human cardiac fibroblast-derived induced pluripotent stem cells expressing cyclin D2 under the myosin heavy chain promoter) used for all hiPSC experiments. This research was funded by grants from National Institutes of Health R01 HL137204 to B.M.O.; National Institutes of Health R01 AR075413 to M.K.; National Institutes of Health Stem Cell Biology T32 GM113846-09 to M.L.H. Dinnaken Fellowship Funding by PACCS Division, Department of Medicine, University of Minnesota to M.L.H. and National Science Foundation GRFP to S.G. Publisher Copyright: {\textcopyright} 2022 The Authors",

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AU - Hall, Mikayla L.

AU - Givens, Sophie

AU - Santosh, Natasha

AU - Iacovino, Michelina

AU - Kyba, Michael

AU - Ogle, Brenda M.

N1 - Funding Information: We would like to thank the Srivastava lab, University of California, San Francisco, for providing the miPSCs used in this study. We would also like to thank the Zhang Lab at the University of Alabama at Birmingham for providing the cell line hciPSC-MHC-CCND2 (human cardiac fibroblast-derived induced pluripotent stem cells expressing cyclin D2 under the myosin heavy chain promoter) used for all hiPSC experiments. This research was funded by grants from National Institutes of Health R01 HL137204 to B.M.O.; National Institutes of Health R01 AR075413 to M.K.; National Institutes of Health Stem Cell Biology T32 GM113846-09 to M.L.H. Dinnaken Fellowship Funding by PACCS Division, Department of Medicine, University of Minnesota to M.L.H. and National Science Foundation GRFP to S.G. Publisher Copyright: © 2022 The Authors

PY - 2022/3/8

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N2 - The extracellular matrix (ECM) provides essential cues to promote endothelial specification during tissue development in vivo; correspondingly, ECM is considered essential for endothelial differentiation outside of the body. However, systematic studies to assess the precise contribution of individual ECM proteins to endothelial differentiation have not been conducted. Further, the multi-component nature of differentiation protocols makes it challenging to study the underlying mechanisms by which the ECM contributes to cell fate. In this study, we determined that Laminin 411 alone increases endothelial differentiation of induced pluripotent stem cells over collagen I or Matrigel. The effect of ECM was shown to be independent of vascular endothelial growth factor (VEGF) binding capacity. We also show that ECM-guided endothelial differentiation is dependent on activation of focal adhesion kinase (FAK), integrin-linked kinase (ILK), Notch, and β-catenin pathways. Our results indicate that ECM contributes to endothelial differentiation through multiple avenues, which converge at the expression of active β-catenin.

AB - The extracellular matrix (ECM) provides essential cues to promote endothelial specification during tissue development in vivo; correspondingly, ECM is considered essential for endothelial differentiation outside of the body. However, systematic studies to assess the precise contribution of individual ECM proteins to endothelial differentiation have not been conducted. Further, the multi-component nature of differentiation protocols makes it challenging to study the underlying mechanisms by which the ECM contributes to cell fate. In this study, we determined that Laminin 411 alone increases endothelial differentiation of induced pluripotent stem cells over collagen I or Matrigel. The effect of ECM was shown to be independent of vascular endothelial growth factor (VEGF) binding capacity. We also show that ECM-guided endothelial differentiation is dependent on activation of focal adhesion kinase (FAK), integrin-linked kinase (ILK), Notch, and β-catenin pathways. Our results indicate that ECM contributes to endothelial differentiation through multiple avenues, which converge at the expression of active β-catenin.

KW - beta catenin

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KW - extracellular matrix

KW - focal adhesion

KW - laminin

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Laminin 411 mediates endothelial specification via multiple signaling axes that converge on β-catenin

Abstract

Bibliographical note

Keywords

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