LYL1 is critical for adult hematopoietic stem cell-derived B and T lymphopoiesis.

Hematopoietic stem cells (HSCs) are defined by their remarkable self-renewal and differentiation capacities, giving rise to progenitors that generate diverse blood and immune cell lineages through the tightly regulated process of hematopoiesis. This process is governed by key transcription factors that control gene expression programs essential for cellular homeostasis, differentiation, and lineage commitment. The transcription factor Lyl1 plays a critical role in regulating HSC function and the lineage specification of hematopoietic progenitors. To investigate its role in adult hematopoiesis, we developed a novel conditional Lyl1 knockout (KO) mouse model. Conditional deletion of Lyl1 in adult mice resulted in reduced HSC and lymphoid progenitor populations, consistent with findings from constitutive Lyl1 KO models. Despite these reductions, mature B- and T-lymphocyte numbers remained unchanged, in contrast to previous reports from embryonically deleted Lyl1 models. Competitive transplantation assays further confirmed that Lyl1 is essential for the generation of adult HSC-derived lymphoid progenitors that support adaptive T- and B-cell production. Our new conditional Lyl1 KO model provides a valuable tool for dissecting Lyl1 function across developmental stages and uncovering the mechanisms that maintain postnatal hematopoietic homeostasis.