Tenascin C promotes hematoendothelial development and T lymphoid commitment from human pluripotent stem cells in chemically defined conditions

Gene Uenishi, Derek Theisen, Jeong-Hee Lee, Akhilesh Kumar, Matt Raymond, Maxim Vodyanik, Scott Swanson, Ron Stewart, James Thomson, Igor Slukvin

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1073-84
Number of pages12
JournalStem Cell Reports
Volume3
Issue number6
DOIs
StatePublished - Dec 9 2014
Externally publishedYes

Bibliographical note

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation/genetics
  • Cell Lineage
  • Cells, Cultured
  • Cluster Analysis
  • Coculture Techniques
  • Culture Media
  • Gene Expression Profiling
  • Hemangioblasts/cytology
  • Hematopoiesis/genetics
  • Humans
  • Mesoderm/cytology
  • Mice
  • Pluripotent Stem Cells/cytology
  • Precursor Cells, T-Lymphoid/cytology
  • Stromal Cells
  • Tenascin/genetics
  • Transcriptome

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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