Altered Expression of microRNAs Implicated in Hematopoietic Dysfunction in the Extracellular Vesicles of Bone Marrow-Mesenchymal Stromal Cells in Aplastic Anemia

Abstract

Recently, we have reported that extracellular vesicles (EVs) from the bone marrow mesenchymal stromal cells (BM-MSC) of aplastic anemia (AA) patients inhibit hematopoietic stem and progenitor cell (HSPC) proliferative and colony-forming ability and promote apoptosis. One mechanism by which AA BM-MSC EVs might contribute to these altered HSPC functions is through microRNAs (miRNAs) encapsulated in EVs. However, little is known about the role of BM-MSC EV-derived miRNAs in regulating HSPC functions in AA. Therefore, we performed miRNA profiling of EVs from BM-MSC of AA (n=6) and normal controls (NC) (n=6), to identify differentially expressed miRNAs carried in AA BM-MSC EVs. DEseq2 analysis identified 34 significantly altered mature miRNAs in AA BM-MSC EVs. Analysis of transcriptome dataset of AA HSPC genes identified that 235 differentially expressed HSPC genes were targeted by these 34 EV miRNAs. The pathway enrichment analysis of 235 HSPC genes revealed their involvement in pathways associated with cell cycle, proliferation, apoptosis, and hematopoiesis regulation, thus highlighting that AA BM-MSC EV miRNAs could potentially contribute to impaired HSPC functions in AA.