Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96277 https://orcid.org/0000-0001-5478-1568 https://orcid.org/0000-0003-2442-5671 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1811074808840978432 |
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| author | 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 Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program 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 Young, Richard A. |
| author_sort | Cassady, John P. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:55:50Z |
| format | Article |
| id | mit-1721.1/96277 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:55:50Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/962772022-09-30T17:46:36Z Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells 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 Young, Richard A. 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 Dani, Vardhan Fan, Zi Peng Sur, Mriganka Young, Richard A. Cassady, John P. Jaenisch, Rudolf 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. Howard Hughes Medical Institute (Gilliam Fellowship) National Institutes of Health (U.S.) (Grant HD045022) National Institutes of Health (U.S.) (Grant R37CA084198) National Institutes of Health (U.S.) (Grant HG002668) Simons Foundation (Grant SFARI 204106) 2015-03-31T15:37:32Z 2015-03-31T15:37:32Z 2014-11 2014-10 Article http://purl.org/eprint/type/JournalArticle 22136711 http://hdl.handle.net/1721.1/96277 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. https://orcid.org/0000-0001-5478-1568 https://orcid.org/0000-0003-2442-5671 https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1016/j.stemcr.2014.10.001 Stem Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/3.0/ application/pdf Elsevier Elsevier |
| spellingShingle | 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 Young, Richard A. Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells |
| title | Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells |
| title_full | Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells |
| title_fullStr | Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells |
| title_full_unstemmed | Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells |
| title_short | Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells |
| title_sort | direct lineage conversion of adult mouse liver cells and b lymphocytes to neural stem cells |
| url | http://hdl.handle.net/1721.1/96277 https://orcid.org/0000-0001-5478-1568 https://orcid.org/0000-0003-2442-5671 https://orcid.org/0000-0001-8855-8647 |
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