Identification of osteolineage cell-derived extracellular vesicle cargo implicated in hematopoietic support

Osteolineage cell-derived extracellular vesicles (EVs) play a regulatory role in hematopoiesis and have been shown to promote the ex vivo expansion of human hematopoietic stem and progenitor cells (HSPCs). Here, we demonstrate that EVs from different human osteolineage sources do not have the same HSPC expansion promoting potential. Comparison of stimulatory and non-stimulatory osteolineage EVs by next-generation sequencing and mass spectrometry analyses revealed distinct microRNA (miRNA) and protein signatures identifying EV-derived candidate regulators of ex vivo HSPC expansion. Accordingly, the treatment of umbilical cord blood-derived CD34+ HSPCs with stimulatory EVs altered HSPC transcriptome, including genes with known roles in cell proliferation. An integrative bioinformatics approach, which connects the HSPC gene expression data with the candidate cargo in stimulatory EVs, delineated the potentially targeted biological functions and pathways during hematopoietic cell expansion and development. In conclusion, our study gives novel insights into the complex biological role of EVs in osteolineage cell-HSPC crosstalk and promotes the utility of EVs and their cargo as therapeutic agents in regenerative medicine. Examination of the effect of extracellular vesicles on hematopoietic stem cells

骨系细胞衍生的细胞外囊泡（extracellular vesicles, EVs）在造血调控中发挥重要作用，且已有研究证实其可促进人类造血干祖细胞（hematopoietic stem and progenitor cells, HSPCs）的体外扩增。本研究证实，不同人类骨系来源的细胞外囊泡，其促HSPC扩增的潜能并不一致。通过下一代测序与质谱分析对比具有促扩增活性与非活性的骨系EVs，发现二者具有显著差异的微小RNA（microRNA, miRNA）与蛋白质谱特征，由此鉴定出可调控HSPC体外扩增的EV源性候选调控因子。采用具有促扩增活性的EVs处理脐带血来源的CD34阳性HSPCs，可改变HSPC的转录组表达谱，其中包含已知参与细胞增殖过程的功能基因。本研究采用整合生物信息学方法，将HSPC基因表达数据与活性EVs中的候选载荷分子进行关联，阐明了造血细胞扩增与发育过程中潜在的靶向生物学功能及通路。综上，本研究为解析骨系细胞与HSPC之间的细胞串扰中EVs的复杂生物学角色提供了全新视角，并推动了EVs及其载荷作为再生医学治疗制剂的应用潜力。细胞外囊泡对造血干细胞的作用研究