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

Stem Cell Reports. 2022 Mar 8;17(3):569-583. doi: 10.1016/j.stemcr.2022.01.005. Epub 2022 Feb 3.

Authors

Mikayla L Hall¹, Sophie Givens¹, Natasha Santosh², Michelina Iacovino², Michael Kyba³, Brenda M Ogle⁴

Affiliations

¹ Department of Biomedical Engineering, University of Minnesota, Twin Cities, 7-130 Nils Hasselmo Hall, 312 Church St. SE, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
² Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
³ Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
⁴ Department of Biomedical Engineering, University of Minnesota, Twin Cities, 7-130 Nils Hasselmo Hall, 312 Church St. SE, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Institute for Engineering in Medicine, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA. Electronic address: ogle@umn.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Extracellular Matrix / metabolism
Laminin* / metabolism
Signal Transduction / physiology
Vascular Endothelial Growth Factor A / metabolism
beta Catenin* / metabolism

Substances

Laminin
Vascular Endothelial Growth Factor A
beta Catenin

Abstract

Publication types

MeSH terms

Substances

Grants and funding