Role of the histone demethylase KDM2B in hematopoietic homeostasis and malignancies [Kras background mouse gene expression]

Development of the hematopoietic system is dynamically controlled by the interplay of transcriptional and epigenetic networks to determine cellular identity. Those networks are critical for homeostasis and frequently dysregulated in leukemias. We identified histone demethylase Kdm2b as a critical regulator of definitive hematopoiesis and lineage specification of hematopoietic stem and progenitor cells (HSPCs). RNA sequencing in murine HSPCs and genome-wide chromatin immunoprecipitation studies in human leukemias revealed that Kdm2b regulates differentiation, lineage choice, cytokine signaling, and quiescence. Comparison of gene expression in wild-type and knockout HSPCs We analyzed lineage depleted cells isolated from bone marrow from mice that express oncogenic Kras in the context of knockout and overexpression of Kdm2b in Affymetrxi GeneChip® Mouse Gene 2.0 ST Array