Journal
CELL REPORTS
Volume 2, Issue 6, Pages 1722-1735Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2012.11.003
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Funding
- National Institutes of Health [U01 HL100395, CIHR MOP93569]
- Canadian Institutes of Health Research [HOP83070, MOP12927]
- Ontario HIV Treatment Network (OHTN)
- Terry Fox Foundation
- Krembil Foundation
- Magna-Golftown Postdoctoral Fellowship at the McEwen Centre for Regenerative Medicine, Toronto
- McMurrich Postdoctoral Fellowship at the McEwen Centre for Regenerative Medicine, Toronto
- OHTN
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The efficient generation of hematopoietic stem cells from human pluripotent stem cells is dependent on the appropriate specification of the definitive hematopoietic program during differentiation. In this study, we used T lymphocyte potential to track the onset of definitive hematopoiesis from human embryonic and induced pluripotent stem cells differentiated with specific morphogens in serum- and stromal-free cultures. We show that this program develops from a progenitor population with characteristics of hemogenic endothelium, including the expression of CD34, VE-cadherin, GATA2, LMO2, and RUNX1. Along with T cells, these progenitors display the capacity to generate myeloid and erythroid cells. Manipulation of Activin/Nodal signaling during early stages of differentiation revealed that development of the definitive hematopoietic progenitor population is not dependent on this pathway, distinguishing it from primitive hematopoiesis. Collectively, these findings demonstrate that it is possible to generate T lymphoid progenitors from pluripotent stem cells and that this lineage develops from a population whose emergence marks the onset of human definitive hematopoiesis.
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