Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells
Name
Cassady-2014-Direct lineage conve.pdf
Size
3.45 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Cassady, John P.
D’Alessio, Ana C.
Sarkar, Sovan
Fan, Zi Peng
Ganz, Kibibi
Roessler, Reinhard
Sur, Mriganka
Young, Richard A.
Jaenisch, Rudolf
Dani, Vardhan
Date Issued
November 2014
Journal
Stem Cell Reports
Publisher
Elsevier
Citation
Cassady, John P. et al. “Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells.” Stem Cell Reports 3.6 (2014): 948–956.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1016/j.stemcr.2014.10.001
