The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors

Fabian Zohren, George P. Souroullas, Min Luo, Ulrike Gerdemann, Maria R. Imperato, Nicola K. Wilson, Berthold Göttgens, Georgi L. Lukov, Margaret A. Goodell

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish
Pages (from-to)761-769
Number of pages9
JournalNature immunology
Volume13
Issue number8
DOIs
StatePublished - Aug 2012

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