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Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-Mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation
The neural crest gives rise to progeny as diverse as peripheral neurons, myelinating cells, cranial muscle, bone and cartilage tissues, and melanocytes. Neural crest derivation encompasses complex morphological change, including epithelial-to-mesenchymal transition (EMT) and migration to the eventua...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622562/ https://www.ncbi.nlm.nih.gov/pubmed/35727432 http://dx.doi.org/10.1007/s12015-022-10393-1 |
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author | Thomas, Ria Menon, Vishal Mani, Rakesh Pruszak, Jan |
author_facet | Thomas, Ria Menon, Vishal Mani, Rakesh Pruszak, Jan |
author_sort | Thomas, Ria |
collection | PubMed |
description | The neural crest gives rise to progeny as diverse as peripheral neurons, myelinating cells, cranial muscle, bone and cartilage tissues, and melanocytes. Neural crest derivation encompasses complex morphological change, including epithelial-to-mesenchymal transition (EMT) and migration to the eventual target locations throughout the body. Neural crest cultures derived from stem cells provide an attractive source for developmental studies in human model systems, of immediate biomedical relevance for neurocristopathies, neural cancer biology and regenerative medicine, if only appropriate markers for lineage and cell type definition and quality control criteria were available. Implementing a defined, scalable protocol to generate neural crest cells from embryonic stem cells, we identify stage-defining cluster-of-differentiation (CD) surface markers during human neural crest development in vitro. Acquisition of increasingly mesenchymal phenotype was characterized by absence of neuroepithelial stemness markers (CD15, CD133, CD49f) and by decrease of CD57 and CD24. Increased per-cell-expression of CD29, CD44 and CD73 correlated with established EMT markers as determined by immunofluorescence and immunoblot analysis. The further development towards migratory neural crest was associated with decreased CD24, CD49f (ITGA6) and CD57 (HNK1) versus an enhanced CD49d (ITGA4), CD49e (ITGA5) and CD51/CD61 (ITGAV/ITGB3) expression. Notably, a shift from CD57 to CD51/CD61 was identified as a sensitive surrogate surface indicator of EMT in neural crest in vitro development. The reported changes in glycan epitope and integrin surface expression may prove useful for elucidating neural crest stemness, EMT progression and malignancies. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12015-022-10393-1. |
format | Online Article Text |
id | pubmed-9622562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-96225622022-11-02 Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-Mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation Thomas, Ria Menon, Vishal Mani, Rakesh Pruszak, Jan Stem Cell Rev Rep Article The neural crest gives rise to progeny as diverse as peripheral neurons, myelinating cells, cranial muscle, bone and cartilage tissues, and melanocytes. Neural crest derivation encompasses complex morphological change, including epithelial-to-mesenchymal transition (EMT) and migration to the eventual target locations throughout the body. Neural crest cultures derived from stem cells provide an attractive source for developmental studies in human model systems, of immediate biomedical relevance for neurocristopathies, neural cancer biology and regenerative medicine, if only appropriate markers for lineage and cell type definition and quality control criteria were available. Implementing a defined, scalable protocol to generate neural crest cells from embryonic stem cells, we identify stage-defining cluster-of-differentiation (CD) surface markers during human neural crest development in vitro. Acquisition of increasingly mesenchymal phenotype was characterized by absence of neuroepithelial stemness markers (CD15, CD133, CD49f) and by decrease of CD57 and CD24. Increased per-cell-expression of CD29, CD44 and CD73 correlated with established EMT markers as determined by immunofluorescence and immunoblot analysis. The further development towards migratory neural crest was associated with decreased CD24, CD49f (ITGA6) and CD57 (HNK1) versus an enhanced CD49d (ITGA4), CD49e (ITGA5) and CD51/CD61 (ITGAV/ITGB3) expression. Notably, a shift from CD57 to CD51/CD61 was identified as a sensitive surrogate surface indicator of EMT in neural crest in vitro development. The reported changes in glycan epitope and integrin surface expression may prove useful for elucidating neural crest stemness, EMT progression and malignancies. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12015-022-10393-1. Springer US 2022-06-21 2022 /pmc/articles/PMC9622562/ /pubmed/35727432 http://dx.doi.org/10.1007/s12015-022-10393-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Thomas, Ria Menon, Vishal Mani, Rakesh Pruszak, Jan Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-Mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation |
title | Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-Mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation |
title_full | Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-Mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation |
title_fullStr | Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-Mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation |
title_full_unstemmed | Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-Mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation |
title_short | Glycan Epitope and Integrin Expression Dynamics Characterize Neural Crest Epithelial-to-Mesenchymal Transition (EMT) in Human Pluripotent Stem Cell Differentiation |
title_sort | glycan epitope and integrin expression dynamics characterize neural crest epithelial-to-mesenchymal transition (emt) in human pluripotent stem cell differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622562/ https://www.ncbi.nlm.nih.gov/pubmed/35727432 http://dx.doi.org/10.1007/s12015-022-10393-1 |
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