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Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263995/ https://www.ncbi.nlm.nih.gov/pubmed/25448067 http://dx.doi.org/10.1016/j.stemcr.2014.09.014 |
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author | Uenishi, Gene Theisen, Derek Lee, Jeong-Hee Kumar, Akhilesh Raymond, Matt Vodyanik, Maxim Swanson, Scott Stewart, Ron Thomson, James Slukvin, Igor |
author_facet | Uenishi, Gene Theisen, Derek Lee, Jeong-Hee Kumar, Akhilesh Raymond, Matt Vodyanik, Maxim Swanson, Scott Stewart, Ron Thomson, James Slukvin, Igor |
author_sort | Uenishi, Gene |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4263995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-42639952014-12-13 Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions Uenishi, Gene Theisen, Derek Lee, Jeong-Hee Kumar, Akhilesh Raymond, Matt Vodyanik, Maxim Swanson, Scott Stewart, Ron Thomson, James Slukvin, Igor Stem Cell Reports Article 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. Elsevier 2014-10-23 /pmc/articles/PMC4263995/ /pubmed/25448067 http://dx.doi.org/10.1016/j.stemcr.2014.09.014 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Uenishi, Gene Theisen, Derek Lee, Jeong-Hee Kumar, Akhilesh Raymond, Matt Vodyanik, Maxim Swanson, Scott Stewart, Ron Thomson, James Slukvin, Igor Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions |
title | Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions |
title_full | Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions |
title_fullStr | Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions |
title_full_unstemmed | Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions |
title_short | Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions |
title_sort | tenascin c promotes hematoendothelial development and t lymphoid commitment from human pluripotent stem cells in chemically defined conditions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263995/ https://www.ncbi.nlm.nih.gov/pubmed/25448067 http://dx.doi.org/10.1016/j.stemcr.2014.09.014 |
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