title: The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors.
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.
authors: Department of Haematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
authors: Fabian
authors: F
authors: Zohren
authors: George P
authors: GP
authors: Souroullas
authors: Min
authors: M
authors: Luo
authors: Ulrike
authors: U
authors: Gerdemann
authors: Maria R
authors: MR
authors: Imperato
authors: Nicola K
authors: NK
authors: Wilson
authors: Berthold
authors: B
authors: Göttgens
authors: Georgi L
authors: GL
authors: Lukov
authors: Margaret A
authors: MA
authors: Goodell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000502:physiology; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000502:physiology*; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D060168:Thymocytes / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C079873:Gfi1 protein, mouse; C490130:Lyl1 protein, mouse