Cell-cell communication is a crucial event during neural development and differentiation. Extracellular membrane vesicles, including exosomes, have been recently discovered to play an important role in these events. Exosomes originate from multivescicular bodies, which may fuse with the plasma membrane and release exosomes in the extracellular space. Exosomes may contain proteins and nucleic acids and can either reach the blood flow and be transported all over the organism, or can fuse with the plasma membrane of other cells and release their content into the target cell. They have been demonstrated to exhert an influence on a large number of biological functions and to be implicated in the progression of several pathologies. They may also play an important role during tissue development, and we have been specifically interested to investigate their role in neural differentiation. Neural stem progenitor cells (NSPCs), obtained from E13,5 embyos, can be maintained in culture under proliferating conditions (i.e. in the presence of bFGF and EGF). Upon treatments with growth factors they may differentiate towards neuronal or glial phenotypes, or both. In this work we were interested in determining whether NSPCs can produce and secrete exosomes and if exosome content may exhert a developmental effect on proliferating and differentiated cells. The capability of these cells to produce and release exosomes was assessed by analyzing the presence of specific markers, such as CD63 and TSG101. Our results indicate that cultured NSPCs produce and secrete exosomes both under proliferating conditions as well as when they are cultured in differentiation medium (e.g. upon removal of EGF). Treatment of proliferating NSPCs with exosomes derived from differentiated cells triggers cell differentiation, as demonstrated by glial and neuronal marker expression; the expression of these markers is also enhanced when exosomes are added to differentiated NSPCs cultures. We also show that the effects of exosome treatment are dose dependent. Characterization of protein and nucleic acid content of NSPCs exosomes is currently under way
Exosome-induced differentiation of neural stem progenitor cells / Poiana, Giancarlo; Stronati, Eleonora; Conti, Roberta; Boussadia, Zaira; Sargiacomo, Massimo; Cacci, Emanuele; Biagioni, Stefano. - (2017), pp. ---. (Intervento presentato al convegno 47th Annual Meeting American Society for Neuroscience 2017 tenutosi a Washington D.C., U.S.A. nel 11-15 novembre 2017).
Exosome-induced differentiation of neural stem progenitor cells
POIANA, Giancarlo;STRONATI, ELEONORA;BOUSSADIA, ZAIRA;CACCI, Emanuele;BIAGIONI, Stefano
2017
Abstract
Cell-cell communication is a crucial event during neural development and differentiation. Extracellular membrane vesicles, including exosomes, have been recently discovered to play an important role in these events. Exosomes originate from multivescicular bodies, which may fuse with the plasma membrane and release exosomes in the extracellular space. Exosomes may contain proteins and nucleic acids and can either reach the blood flow and be transported all over the organism, or can fuse with the plasma membrane of other cells and release their content into the target cell. They have been demonstrated to exhert an influence on a large number of biological functions and to be implicated in the progression of several pathologies. They may also play an important role during tissue development, and we have been specifically interested to investigate their role in neural differentiation. Neural stem progenitor cells (NSPCs), obtained from E13,5 embyos, can be maintained in culture under proliferating conditions (i.e. in the presence of bFGF and EGF). Upon treatments with growth factors they may differentiate towards neuronal or glial phenotypes, or both. In this work we were interested in determining whether NSPCs can produce and secrete exosomes and if exosome content may exhert a developmental effect on proliferating and differentiated cells. The capability of these cells to produce and release exosomes was assessed by analyzing the presence of specific markers, such as CD63 and TSG101. Our results indicate that cultured NSPCs produce and secrete exosomes both under proliferating conditions as well as when they are cultured in differentiation medium (e.g. upon removal of EGF). Treatment of proliferating NSPCs with exosomes derived from differentiated cells triggers cell differentiation, as demonstrated by glial and neuronal marker expression; the expression of these markers is also enhanced when exosomes are added to differentiated NSPCs cultures. We also show that the effects of exosome treatment are dose dependent. Characterization of protein and nucleic acid content of NSPCs exosomes is currently under wayI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.