Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions
| Autor: | Scott Swanson, Jeong Hee Lee, James A. Thomson, Igor I. Slukvin, Maxim A. Vodyanik, Derek J. Theisen, Gene Uenishi, Akhilesh Kumar, Matt Raymond, Ron Stewart |
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| Rok vydání: | 2014 |
| Předmět: |
Pluripotent Stem Cells
Myeloid Hemangioblasts Cell Culture Techniques Biology Biochemistry Article Mesoderm Mice 03 medical and health sciences 0302 clinical medicine Genetics medicine Animals Cluster Analysis Humans Cell Lineage Progenitor cell Induced pluripotent stem cell lcsh:QH301-705.5 Cells Cultured 030304 developmental biology Hemogenic endothelium lcsh:R5-920 Precursor Cells T-Lymphoid 0303 health sciences Gene Expression Profiling Tenascin C Cell Differentiation Tenascin Cell Biology Coculture Techniques Culture Media Hematopoiesis Cell biology Haematopoiesis medicine.anatomical_structure lcsh:Biology (General) Cell culture 030220 oncology & carcinogenesis Immunology biology.protein Stromal Cells Stem cell lcsh:Medicine (General) Transcriptome Developmental Biology |
| Zdroj: | Stem Cell Reports Stem Cell Reports, Vol 3, Iss 6, Pp 1073-1084 (2014) |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2014.09.014 |
| Popis: | Summary The recent identification of hemogenic endothelium (HE) in human pluripotent stem cell (hPSC) cultures presents opportunities to investigate signaling pathways that are essential for blood development from endothelium and provides an exploratory platform for de novo generation of hematopoietic stem cells (HSCs). However, the use of poorly defined human or animal components limits the utility of the current differentiation systems for studying specific growth factors required for HE induction and manufacturing clinical-grade therapeutic blood cells. Here, we identified chemically defined conditions required to produce HE from hPSCs growing in Essential 8 (E8) medium and showed that Tenascin C (TenC), an extracellular matrix protein associated with HSC niches, strongly promotes HE and definitive hematopoiesis in this system. hPSCs differentiated in chemically defined conditions undergo stages of development similar to those previously described in hPSCs cocultured on OP9 feeders, including the formation of VE-Cadherin+CD73−CD235a/CD43− HE and hematopoietic progenitors with myeloid and T lymphoid potential. Graphical Abstract Highlights • Hemogenic endothelium is generated in a completely defined xenogen-free system • The system reproduces all stages of hematopoietic development • Tenascin C enhances hematoendothelial development from pluripotent stem cells • Tenesacin C uniquely supports T cell specification In this article, Slukvin and colleagues describe a feeder- and xenogene-free chemically defined platform for differentiating human pluripotent stem cells into definitive hematopoietic cells. They find that Tenascin C, a matrix protein associated with hematopoietic stem cell niches, strongly promotes hemogenic endothelium development and T lymphoid commitment in this system. |
| Databáze: | OpenAIRE |
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