title: Direct reprogramming of fibroblasts into neural stem cells by defined factors.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany. dwhan@konkuk.ac.kr
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Han
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
authors.forename: Andreas
authors.initials: A
authors.lastname: Hermann
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hemmer
authors.forename: Susanne
authors.initials: S
authors.lastname: Höing
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Araúzo-Bravo
authors.forename: Holm
authors.initials: H
authors.lastname: Zaehres
authors.forename: Guangming
authors.initials: G
authors.lastname: Wu
authors.forename: Stefan
authors.initials: S
authors.lastname: Frank
authors.forename: Sören
authors.initials: S
authors.lastname: Moritz
authors.forename: Boris
authors.initials: B
authors.lastname: Greber
authors.forename: Ji Hun
authors.initials: JH
authors.lastname: Yang
authors.forename: Hoon Taek
authors.initials: HT
authors.lastname: Lee
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schwamborn
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D054337:Cell Dedifferentiation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors