西亚试剂：首次将皮肤细胞直接转化为神经干细胞

Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors

Dong Wook Han, Natalia Tapia, Andreas Hermann, Kathrin Hemmer, Susanne Höing, Marcos J. Araúzo-Bravo, Holm Zaehres, Guangming Wu, Stefan Frank, Sören Moritz, Boris Greber, Ji Hun Yang, Hoon Taek Lee, Jens C. Schwamborn, Alexander Storch, Hans R. Schöler

Recent studies have shown that defined sets of transcription factors can directly reprogram differentiated somatic cells to a different differentiated cell type without passing through a pluripotent state, but the restricted proliferative and lineage potential of the resulting cells limits the scope of their potential applications. Here we show that a combination of transcription factors (Brn4/Pou3f4, Sox2, Klf4, c-Myc, plus E47/Tcf3) induces mouse fibroblasts to directly acquire a neural stem cell identity—which we term as induced neural stem cells (iNSCs). Direct reprogramming of fibroblasts into iNSCs is a gradual process in which the donor transcriptional program is silenced over time. iNSCs exhibit cell morphology, gene expression, epigenetic features, differentiation potential, and self-renewing capacity, as well as in vitro and in vivo functionality similar to those of wild-type NSCs. We conclude that differentiated cells can be reprogrammed directly into specific somatic stem cell types by defined sets of specific transcription factors.

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