T Lymphocyte Potential Marks the Emergence of Definitive Hematopoietic Progenitors in Human Pluripotent Stem Cell Differentiation Cultures
| Autor: | Juan Carlos Zúñiga-Pflücker, Marion Kennedy, Christopher M. Sturgeon, Gordon Keller, Geneve Awong, Ross LaMotte-Mohs, Andrea Ditadi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Pluripotent Stem Cells
Cellular differentiation T-Lymphocytes CD34 Stem cell factor Biology General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences 0302 clinical medicine Humans Progenitor cell Induced pluripotent stem cell lcsh:QH301-705.5 030304 developmental biology 0303 health sciences Precursor Cells T-Lymphoid Cell Differentiation Embryonic stem cell Antigens Differentiation Cell biology Endothelial stem cell Gene Expression Regulation lcsh:Biology (General) 030220 oncology & carcinogenesis Immunology Stem cell Signal Transduction |
| Zdroj: | Cell Reports, Vol 2, Iss 6, Pp 1722-1735 (2012) |
| ISSN: | 2211-1247 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|