HEBAlt enhances the T-cell potential of fetal myeloid-biased precursors
| Autor: | Carol L. Claus, Paula Rajkumar, Marsela Braunstein, Amanda J. Moore, Duncheng Wang, Michele K. Anderson, Giovanna Vaccarelli |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Myeloid
T-Lymphocytes T cell Immunology Population Biology Ikaros Transcription Factor Mice Fetus Basic Helix-Loop-Helix Transcription Factors medicine Animals Antigens Ly Immunology and Allergy Cell Lineage Receptor Notch1 education Transcription factor Myeloid Progenitor Cells Precursor Cells T-Lymphoid education.field_of_study Membrane Proteins Cell Differentiation General Medicine T lymphocyte Hematopoiesis Up-Regulation Cell biology Proto-Oncogene Proteins c-kit Haematopoiesis medicine.anatomical_structure Liver Signal transduction |
| Zdroj: | International Immunology. 22:963-972 |
| ISSN: | 1460-2377 0953-8178 |
| DOI: | 10.1093/intimm/dxq450 |
| Popis: | Hematopoiesis is controlled by the interplay between transcription factors and environmental signals. One of the primary determinants of the T-lineage choice is Delta-like (DL)-Notch signaling, which promotes T-cell development and inhibits B-cell development. We have found that the transcription factor HEBAlt is up-regulated in early hematopoietic precursors in response to DL-Notch signaling and that it can promote early T-cell development. Here, we identified a population of lineage-negative Sca-1 2 c-kit 1 (LK) cells in the mouse fetal liver that rapidly gave rise to myeloid cells and B cells but exhibited very little T-cell potential. However, forced expression of HEBAlt in these precursors restored their ability to develop into T cells. We also showed that Ikaros and Notch1 are up-regulated in response to HEBAlt over-expression and that activated Notch1 enhances the ability of LK cells to enter the T-cell lineage. Furthermore, the myeloid transcription factor C/EBPa is down-regulated in response to HEBAlt. We therefore propose that HEBAlt plays a role in the network that enforces the T-lineage fate and limits myeloid fate during hematopoiesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|