TIRAP drives myelosuppression through an Ifnγ-Hmgb1 axis that disrupts the endothelial niche.

Purpose: The goals of this study are to compare the transcriptome profile of mouse hematopoietic stem/progenitor cells (HSPC) from the bone marrow overexpressing the innate immune adaptor protein TIRAP to control vector expressing HSPC using RNA-Seq. Methods: mRNA profiles of wild-type (WT) mice bone marrow overexpressing TIRAP or control vectors were generated by deep sequencing, in triplicate, using the Illumina platform. RNA-Seq data were aligned using JAGuaR (v2.0.3), using the mm10 reference. Expression quantification was performed with Sailfish (v0.6.2), using RefSeq gene models. The differential expression analysis between TIRAP expressing bone marrow and control was performed using DESeq2 (v1.10.1). Results: Using an optimized data analysis workflow, we mapped approximately 92% sequenced reads on average per sample to the mouse genome (build mm10). Bone marrow mRNA profiles of wild type (WT) mice overexpressing either TIRAP or control (MIG) vectors.