The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors.
Nat Immunol, 2012/7/08;13(8):761-9.
Zohren F[1], Souroullas GP, Luo M, Gerdemann U, Imperato MR, Wilson NK, Göttgens B, Lukov GL, Goodell MA
Affiliations
PMID: 22772404DOI: 10.1038/ni.2365
Impact factor: 31.25
Abstract
Thymopoiesis depends on the recruitment and expansion of bone marrow-derived progenitor populations; tight regulation of these processes is required for maintenance of the homeostasis of the T lineage. Lyl-1, a transcription factor that regulates hematopoietic progenitors, is expressed in thymocyte progenitors until T cell commitment. Here we demonstrate a requirement for Lyl-1 in lymphoid specification and the maintenance of early T lineage progenitors (ETPs). Lyl-1 deficiency resulted in profound defects in the generation of lymphoid-primed multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs) and ETPs. Lyl-1-deficient ETPs and thymocyte progenitors at the CD4(-)CD8(-) double-negative 2 (DN2) stage showed more apoptosis, blocked differentiation and impaired population expansion. We identified Gfi1 as a critical transcriptional target of Lyl-1-mediated lymphopoiesis of T cells. Thus, Lyl-1 is a pivotal component of a transcriptional program that controls the lymphoid specification and maintenance of ETPs.
MeSH terms
Animals; Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Bone Marrow Cells; CD4 Antigens; CD8 Antigens; Cell Lineage; DNA-Binding Proteins; Lymphoid Progenitor Cells; Lymphopoiesis; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasm Proteins; T-Lymphocytes; Thymocytes; Transcription Factors
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