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Stem Cell Reports. 2014 Dec 9;3(6):948-56. doi: 10.1016/j.stemcr.2014.10.001. Epub 2014 Nov 6.

Direct lineage conversion of adult mouse liver cells and B lymphocytes to neural stem cells.

Author information

1
The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
3
Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
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.

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.

PMID:
25454632
PMCID:
PMC4264067
DOI:
10.1016/j.stemcr.2014.10.001
[Indexed for MEDLINE]
Free PMC Article

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