Transcriptional regulation of hematopoietic stem cell progenitors and acute myeloid leukemia by the IRE1a-XBP1 pathway [KO]

The inositol-requiring enzyme-1a (IRE1a), through its key effector transcription factor X-box binding protein-1 (XBP1), regulates cell fate and malignancy in a tissue and cell-specific manner. Here, we define the transcriptional perturbations associated with IRE1a deficiency in normal murine hematopoieitic stem cell (HSC) progenitors and HSC progenitors expressing Flt3 internal tandem duplication (FLT3-ITD) allele, a myeloid leukemia oncogne. Beyond its classical role in activating genes involved in restoring cellular proteostasis during the unfolded protein response (UPR), our transcriptome analysis reveal XBP1-dependent regulation of genes involved in diverse biological processes required for HSC homeostasis and acute myeloid leukemia (AML) development. Transcriptome of normal and Flt3-ITD expressing hematopoietic cells from murine bone marrow (BM) were determined using TruSeq Stranded mRNA Libraries. The complete data set contains a total of 24 samples comprising triplicates of Lin-Sca1+cKit+ (LSK) and granulocyte-macrophage progenitors (GMP) from the following mouse genotypes: wildtype (WT), Flt3-ITD (ITD), Ern1(fl/fl)-VavCre (IRE1_KO) and Ern1(fl/fl)-VavCre-Flt3-ITD (IRE1_KO_ITD).