Extracellular vesicles of stromal origin target and support hematopoietic stem and progenitor cells

• Published in: The Journal of cell biology Vol. 216; no. 7; pp. 2217 - 2230
• Main Authors: Stik, Gregoire, Crequit, Simon, Petit, Laurence, Durant, Jennifer, Charbord, Pierre, Jaffredo, Thierry, Durand, Charles
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 03.07.2017; The Rockefeller University Press
• Subjects: Animals; Apoptosis; Biochemistry, Molecular Biology; Cancer; Cell Behavior; Cell interactions; Cell Line; Cell Survival; Cells; Cells (biology); Cellular Biology; Coculture Techniques; Development Biology; Embryology and Organogenesis; Extracellular vesicles; Extracellular Vesicles - metabolism; Extracellular Vesicles - secretion; Female; Fetuses; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Developmental; Genetic Markers; Genomics; Hematology; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Human health and pathology; Life Sciences; Liver; Liver - cytology; Liver - metabolism; Liver - secretion; Mesenchyme; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Networks; Molecules; Paracrine Communication; Phenotype; Regenerative medicine; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction; Stem Cell Niche; Stem cells; Stromal cells; Stromal Cells - metabolism; Stromal Cells - secretion; Time Factors; Transcriptome; Transfection; Vesicles
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201601109

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.