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Exosome-mediated direct conversion of human fibroblasts into neural progenitor-like cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98115 | GEO | 2018/04/24

REPOSITORIES: GEO

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Exosome-mediated direct conversion of human fibroblasts into neural progenitor-like cells [WTS]

Project description:Exosome, a kind of extracellular vesicles, has been introduced as a vehicle for horizontal transferring of genetic material. We induced autologous exosome containing a cocktail of reprogramming factors (‘reprosome’) to convert fibroblasts into neural progenitor cells (NPC). The fibroblasts were sonicated and subsequently cultured in NSC media for 1 day to induce release of reprosomes composed of reprogramming factors associated to chromatin remodeling and neural lineage-specific factors. After treated with reprosomes, fibroblasts were converted into NPCs (rNPC) with great efficiency via activation of chromatin remodeling, as fast as it required only five days for formation of 1,500 spheroids showing NPC-like phenotype. The rNPCs maintained self-renewal and proliferative properties for several weeks and successfully differentiated into neuron, astrocyte, and oligodendrocyte, in vitro and in vivo. Reprosome-mediated cellular reprogramming is simple, safe, and efficient, thus providing a new paradigm for clinical application that requires autologous stem cells.

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Exosome-mediated direct conversion of human fibroblasts into neural progenitor-like cells

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Project description:Disorders of the biliary epithelium, known as cholangiopathies, cause severe and irreversible liver diseases. The limited accessibility of bile duct precludes modeling of several cholangiocyte-mediated diseases. Therefore, novel approaches for obtaining functional cholangiocytes with high purity are needed. Previous work has shown that the combination of Hnf1? and Foxa3 could directly convert mouse fibroblasts into bipotential hepatic stem cell-like cells, termed iHepSCs. However, the efficiency of converting fibroblasts into iHepSCs is low, and these iHepSCs exhibit extremely low differentiation potential into cholangiocytes, thus hindering the translation of iHepSCs to the clinic. Here, we describe that the expression of Hnf1? and Foxa3 dramatically facilitates the robust generation of iHepSCs. Notably, prolonged in vitro culture of Hnf1?- and Foxa3-derived iHepSCs induces a Notch signaling-mediated secondary conversion into cholangiocyte progenitor-like cells that display dramatically enhanced differentiation capacity into mature cholangiocytes. Our study provides a robust two-step approach for obtaining cholangiocyte progenitor-like cells using defined factors.

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