Stik Gregoire, Crequit Simon, Petit Laurence, Durant Jennifer, Charbord Pierre, Jaffredo Thierry, Durand Charles
Sorbonne Universités, University Pierre et Marie Curie Paris 06, Centre National de la Recherche Scientifique 7622, Institut National de la Santé et de la Recherche Médicale U 1156, Institute de Biologie Paris Siene, Laboratoire de Biologie du Développement, Paris, France.
Sorbonne Universités, University Pierre et Marie Curie Paris 06, Centre National de la Recherche Scientifique 7622, Institut National de la Santé et de la Recherche Médicale U 1156, Institute de Biologie Paris Siene, Laboratoire de Biologie du Développement, Paris, France
J Cell Biol. 2017 Jul 3;216(7):2217-2230. doi: 10.1083/jcb.201601109. Epub 2017 Jun 19.
Extracellular vesicles (EVs) have been recently reported as crucial mediators in cell-to-cell communication in development and disease. In this study, we investigate whether mesenchymal stromal cells that constitute a supportive microenvironment for hematopoietic stem and progenitor cells (HSPCs) released EVs that could affect the gene expression and function of HSPCs. By taking advantage of two fetal liver-derived stromal lines with widely differing abilities to maintain HSPCs ex vivo, we demonstrate that stromal EVs play a critical role in the regulation of HSPCs. Both supportive and nonsupportive stromal lines secreted EVs, but only those delivered by the supportive line were taken up by HSPCs ex vivo and in vivo. These EVs harbored a specific molecular signature, modulated the gene expression in HSPCs after uptake, and maintained the survival and clonogenic potential of HSPCs, presumably by preventing apoptosis. In conclusion, our study reveals that EVs are an important component of the HSPC niche, which may have major applications in regenerative medicine.
细胞外囊泡（EVs）最近被报道为发育和疾病中细胞间通讯的关键介质。在本研究中，我们调查构成造血干细胞和祖细胞（HSPCs）支持性微环境的间充质基质细胞是否释放能够影响HSPCs基因表达和功能的EVs。通过利用两种在体外维持HSPCs能力差异很大的胎儿肝脏来源的基质细胞系，我们证明基质EVs在HSPCs的调节中起关键作用。支持性和非支持性基质细胞系均分泌EVs，但只有支持性细胞系递送的EVs在体外和体内被HSPCs摄取。这些EVs具有特定的分子特征，摄取后调节HSPCs中的基因表达，并维持HSPCs的存活和克隆潜力，可能是通过防止细胞凋亡。总之，我们的研究表明EVs是HSPC生态位的重要组成部分，这可能在再生医学中有重要应用。
