In this article, Rostovskaya and colleagues established clonal skeletal progenitors with distinct differentiation properties from mouse bone marrow. RNA-seq analysis revealed transcriptional signatures of osteogenic and adipogenic lineages and IFNγ signaling as potential regulator of cell fate commitment. IFNγ is a negative regulator of Egr1 and Egr2 transcription factors. Egr1 maintains adipogenic and Egr2 suppresses osteogenic transcriptional program and commitment.