title: Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.
abstract: Overexpression of transcription factors has been used to directly reprogram somatic cells into a range of other differentiated cell types, including multipotent neural stem cells (NSCs), that can be used to generate neurons and glia. However, the ability to maintain the NSC state independent of the inducing factors and the identity of the somatic donor cells remain two important unresolved issues in transdifferentiation. Here we used transduction of doxycycline-inducible transcription factors to generate stable tripotent NSCs. The induced NSCs (iNSCs) maintained their characteristics in the absence of exogenous factor expression and were transcriptionally, epigenetically, and functionally similar to primary brain-derived NSCs. Importantly, we also generated tripotent iNSCs from multiple adult cell types, including mature liver and B cells. Our results show that self-maintaining proliferative neural cells can be induced from nonectodermal cells by expressing specific combinations of transcription factors.
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Cassady
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Ana C
authors.initials: AC
authors.lastname: D'Alessio
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Sovan
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Vardhan S
authors.initials: VS
authors.lastname: Dani
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Zi Peng
authors.initials: ZP
authors.lastname: Fan
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Kibibi
authors.initials: K
authors.lastname: Ganz
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Roessler
authors.affiliation: Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Mriganka
authors.initials: M
authors.lastname: Sur
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
authors.affiliation: The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: jaenisch@wi.mit.edu.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics; D054338:Cell Transdifferentiation / Q000235:genetics; D065150:Cellular Reprogramming; D016000:Cluster Analysis; D044127:Epigenesis, Genetic; D015870:Gene Expression; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors