NR4A1 and NR4A3 Restrict HSC Proliferation via Reciprocal Regulation of C/EBPa and Inflammatory Signaling

NR4A nuclear receptors are known tumor suppressors of acute myeloid leukemia and are essential regulators of hematopoietic stem cell (HSC) quiescence. To study the transcriptional consequences of acute NR4A1/3 codepletion in HSCs, we used an Nr4a1/3 conditional knockout mouse model and performed a global transcriptome profiling using RNA-Seq in sorted HSCs four days after NR4A1/3 codepletion. Overall design: CDKO mice (Nr4a1 fl/fl; Nr4a3-/-; Rosa26-ERt2) and control mice (Nr4a1 fl/fl; Nr4a3-/-) were treated with 4 daily tamoxifen injections (120 mg/Kg) to incduce Nr4a1 excision and hematopoietic stem cells were sorted on day 5 for RNA-Seq analysis. Each sample consists in a pool of 3-5 mice.