HEBAlt enhances the T-cell potential of fetal myeloid-biased precursors.
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⁻c-kit(+) (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/EBPα 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.
Division of Molecular and Cellular Biology, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada.
Marsela
M
Braunstein
Paula
P
Rajkumar
Carol L
CL
Claus
Giovanna
G
Vaccarelli
Amanda J
AJ
Moore
Duncheng
D
Wang
Michele K
MK
Anderson
D000818:Animals; D000950:Antigens, Ly; D051792:Basic Helix-Loop-Helix Proteins / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D005333:Fetus / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology*; D051740:Ikaros Transcription Factor / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency; D051379:Mice; D023461:Myeloid Progenitor Cells / Q000276:immunology; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D051881:Receptor, Notch1 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D015854:Up-Regulation
D000950:Antigens, Ly; D051792:Basic Helix-Loop-Helix Proteins; D051740:Ikaros Transcription Factor; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; D051881:Receptor, Notch1; C074650:Ly6a protein, mouse; C497762:Notch1 protein, mouse; C489532:Tcf12 protein, mouse; C497238:Zfpn1a1 protein, mouse