Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells
| Autor: | Denis Evseenko, Yuhua Zhu, Katja Schenke-Layland, Jeffrey Kuo, Brooke Latour, Shundi Ge, Jessica Scholes, Gautam Dravid, Xinmin Li, W. Robb MacLellan, Gay M. Crooks |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2010 |
| Předmět: |
Pluripotent Stem Cells
Mesoderm animal structures extracellular matrix Cellular differentiation Germ layer Biology Mice Antigens Neoplasm medicine Animals Humans Cell Lineage Epithelial–mesenchymal transition Progenitor cell Induced pluripotent stem cell hematopoietic development Embryonic Stem Cells Genetics Multidisciplinary cardiovascular Mesenchymal stem cell Gene Expression Regulation Developmental Cell Differentiation Biological Sciences Epithelial Cell Adhesion Molecule embryonic stem cell Embryonic stem cell CD56 Antigen Cell biology medicine.anatomical_structure embryonic structures Cell Adhesion Molecules Biomarkers |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:13742-13747 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1002077107 |
| Popis: | Our understanding of how mesodermal tissue is formed has been limited by the absence of specific and reliable markers of early mesoderm commitment. We report that mesoderm commitment from human embryonic stem cells (hESCs) is initiated by epithelial-to-mesenchymal transition (EMT) as shown by gene expression profiling and by reciprocal changes in expression of the cell surface proteins, EpCAM/CD326 and NCAM/CD56. Molecular and functional assays reveal that the earliest CD326 − CD56 + cells, generated from hESCs in the presence of activin A, BMP4, VEGF, and FGF2, represent a multipotent mesoderm-committed progenitor population. CD326 − CD56 + progenitors are unique in their ability to generate all mesodermal lineages including hematopoietic, endothelial, mesenchymal (bone, cartilage, fat, fibroblast), smooth muscle, and cardiomyocytes, while lacking the pluripotency of hESCs. CD326 − CD56 + cells are the precursors of previously reported, more lineage-restricted mesodermal progenitors. These findings present a unique approach to study how germ layer specification is regulated and offer a promising target for tissue engineering. |
| Databáze: | OpenAIRE |
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