Lyl1 regulates lymphoid specification and maintenance of early T lineage progenitors

Thymopoiesis depends on recruitment and expansion of bone marrow-derived progenitors, tight regulation of which is required to maintain T-lineage homeostasis. Lyl1, a transcription factor regulating hematopoietic progenitors, is expressed in thymocyte progenitors until T cell commitment. Here we demonstrate a requirement for Lyl1 in lymphoid specification and the maintenance of early T lineage progenitors (ETPs). Lyl1 deficiency resulted in profound defects in generation of lymphoid primed multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs) and ETPs. Lyl1-deficient ETPs and DN2 thymocyte progenitors showed increased apoptosis, blocked differentiation and impaired expansion. We identified Gfi1 as a critical transcriptional target of Lyl1-mediated T-lymphopoiesis. Thus, Lyl1 is a pivotal component of a transcriptional program that controls lymphoid specification and maintenance of ETPs.