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Cited by 37Pluripotent Stem Cells ResearchCell Adhesion Molecules ResearchCellular Mechanics and Interactions

Definitive endoderm derived from human embryonic stem cells highly express the integrin receptors αV and β5

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Wong, Jennifer C.Y., Gao, Steven Y., Lees, Justin G., Best, Marie B., Wang, Rennian, Tuch, Bernard E.·2010·Cell Adhesion & Migration
DOI 10.4161/cam.4.1.10627PMC PMC2852556
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Abstract

Human embryonic stem cells (hESCs) can be directed to differentiate into a number of endoderm cell types, however mature functional cells have yet to be produced in vitro. This suggests that there may be important factors that have yet to be described, which may be essential for the proper derivation of these cells. One such factor is the integrin mediated interactions between a cell and the extracellular matrix (ECM). On this basis, the present study investigated the role of the ECM in the directed differentiation of hESCs to definitive endoderm via analysis of integrin gene expression. The results showed that definitive endoderm can be efficiently and effectively derived from hESCs in a feeder free, single defined ECM of laminin. Analysis of integrin expression also showed that definitive endoderm highly express the integrins alphaV and beta5, which have the ability to bind to vitronectin, whilst expression of the pluripotency related laminin binding integrins alpha3, alpha6 and beta4 were downregulated. This suggested a potential role of vitronectin binding integrins in the development of definitive endoderm.

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  • Stem cell maturation, differentiation, and derived cell function depend critically on temporal and spatial engagement of cell surface integrins with ECM in development and ex vivo culture.

    “There is now clear evidence from our group and the work of others that stem cell maturation and differentiation and the proper function of cells derived thereof are critically dependent on the temporal and spatial engagement of cell surface integrins with extracellular matrices (ECM) both in a given organ system during development19 and in the context of ex vivo stem cell culture20–27.”

    From In situ expansion, differentiation, and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid (2020) · cites this paper as [20]

    The Introduction (page not provided) says integrin-mediated interactions are vital to normal cell function and differentiation, and the Results & Discussion report changes in integrin expression as human embryonic stem cells form definitive endoderm. The paper does not establish that maturation and the function of derived cells critically depend on the temporal and spatial engagement of integrins with ECM; it describes the proposed role of the observed integrins as requiring further investigation. (LLM, conf=0.84)

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Research works printed but not linked: 11

  1. [7]7. Herard AL, Pierrot D, Hinnrasky J, Kaplan H, Sheppard D, Puchelle E, Zahm JM. Fibronectin and its alpha5beta1-integrin receptor are involved in the wound-repair process of airway epithelium. Am J Physiol 1996; 271:726-33.
  2. [9]9. Charo IF, Nannizzi L, Smith JW, Cheresh DA. The vitronectin receptor alphavbeta3 binds fibronectin and acts in concert with alpha5beta1 in promoting cellular attachment and spreading on fibronectin. J Cell Biol 1990; 111:2795-800.
  3. [12]12. Shaw LM, Mercurio AM. Regulation of alpha6beta1 integrin laminin receptor function by the cytoplas- mic domain of the alpha6 subunit. J Cell Biol 1993; 123:1017-25.
  4. [13]13. Shaw LM, Messier JM, Mercurio AM. The activa- tion dependent adhesion of macrophages to laminin involves cytoskeletal anchoring and phosphorylation of the alpha6beta1 integrin. J Cell Biol 1990; 110:2167- 74.
  5. [15]15. Wayner EA, Orlando RA, Cheresh DA. Integrins alphavbeta3 and alphavbeta5 contribute to cell attach- ment to vitronectin but differentially distribute on the cell surface. J Cell Biol 1991; 113:919-29.
  6. [17]17. Lee EC, Lotz MM, Steele GD Jr, Mercurio AM. The integrin alpha6beta4 is a laminin receptor. J Cell Biol 1992; 117:671-8.
  7. [18]18. Chang AC, Salomon DR, Wadsworth S, Hong MJ, Mojcik CF, Otto S, et al. Alpha3beta1 and alpha6beta1 integrins mediate laminin/merosin binding and func- tion as costimulatory molecules for human thymocyte proliferation. J Immunol 1995; 154:500-10.
  8. [22]22. Wells JM, Melton DA. Vertebrate endoderm develop- ment. Annu Rev Cell Dev Biol 1999; 15:393-410.
  9. [33]33. Wang R, Li J, Lyte K, Yashpal NK, Fellows F, Goodyer CG. Role for beta1 integrin and its associated alpha3, alpha5 and alpha6 subunits in development of the human fetal pancreas. Diabetes 2005; 54:2080-9.
  10. [34]34. Luzina IG, Todd NW, Nacu N, Lockatell V, Choi J, Hummers LK, Atamas SP. Regulation of pulmonary inflammation and fibrosis through expression of inte- grins alphaVbeta3 and alphaVbeta5 on pulmonary T lymphocytes. Arthritis Rheum 2009; 60:1530-9.
  11. [39]39. Tulla M, Pentikainen OT, Viitasalo T, Kapyla J, Impola U, Nykvist P, et al. Selective binding of collagen subtypes by integrin alpha1I, alpha2I and alpha10I domains. J Biol Chem 2001; 276:48206-12.

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Authors
Wong, J. C. Y., Gao, S. Y., Lees, J. G., Best, M. B., Wang, R., & Tuch, B. E.
Affiliations
  • UNSW Sydney (AU)
  • Western University (CA)
Corresponding author
Wong, Jennifer C.Y.
ORCID
Venue
Cell Adhesion & Migration
Publisher
Informa UK Limited
Published
2010-01
Volume
4
Issue
1
Pages
39-45
ISSN
  • 1933-6918 (ISSN-L)
  • 1933-6926
DOI
10.4161/cam.4.1.10627
PMC
PMC2852556
OpenAlex
W1990683187
Cited by
37
References
41
Citations by year
2026: 3 · 2025: 4 · 2024: 1 · 2022: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 8 · 2013: 4 · 2012: 1
FWCI
1.56
Type
journal article
Language
en
Open access
Locations
  • Cell Adhesion & Migration (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Scholarship@Western (Western University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
definitive endoderm, human embryonic stem cells, ITGAV, integrin beta5, vitronectin, laminin, extracellular matrix, feeder-free differentiation, defined culture conditions, pluripotency, integrin expression
MeSH terms
Cell Differentiation, Cell Line, Collagen, Drug Combinations, Endoderm, Extracellular Matrix, Humans, Laminin, Protein Binding, Proteoglycans, Gene Expression Regulation, Developmental, Integrin beta1, Vitronectin, Reverse Transcriptase Polymerase Chain Reaction, Integrin alpha6, Integrin alphaV, Integrin beta Chains, Embryonic Stem Cells

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