Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors

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• 作者：Dong  ; Wook Han¹ ; ² ; ⁷ ; ^{dwhan@konkuk.ac.kr} ; Natalia Tapia¹ ; ⁷ ; Andreas Hermann³ ; ⁴ ; Kathrin Hemmer⁵ ; Susanne Hö ; ing¹ ; Marcos  ; J. Araú ; zo-Bravo¹ ; Holm Zaehres¹ ; Guangming Wu¹ ; Stefan Frank¹ ; Sö ; ren Moritz¹ ; Boris Greber¹ ; Ji  ; Hun Yang¹ ; Hoon  ; Taek Lee² ; Jens  ; C. Schwamborn⁵ ; Alexander Storch³ ; ⁴ ; Hans  ; R. Schö ; ler¹ ; ⁶ ; ^{office@mpi-muenster.mpg.de}
• 刊名：Cell Stem Cell
• 出版年：2012
• 出版时间：6 April, 2012
• 年：2012
• 卷：10
• 期：4
• 页码：465-472
• 全文大小：1616 K

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Summary

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¡ªwhich 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.