LMO2 is essential to maintain the ability of progenitors to differentiate into T-cell lineage in mice.

Notch signaling primarily determines T-cell fate. However, the molecular mechanisms underlying the maintenance of T-lineage potential in pre-thymic progenitors remain unclear. Here, we established two murine -deficient pro-B cell lines, with and without T-lineage potential. The latter expressed lower levels of ; their potential was restored via ectopic expression of . Conversely, the CRISPR/Cas9-mediated deletion of resulted in the loss of the T-lineage potential. Introduction of rescued massive cell death of Notch-stimulated pro-B cells without efficient LMO2-driven expression but was not sufficient to retain their T-lineage potential. Pro-B cells without T-lineage potential failed to activate due to DNA methylation; transduction restored this capacity. Moreover, direct binding of LMO2 to the and loci was observed. Altogether, our results highlight LMO2 as a crucial player in the survival and maintenance of T-lineage potential in T-cell progenitors via the regulation of the expression of and .