Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors
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...
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| Veröffentlicht in: | Cell stem cell 2012-04, Vol.10 (4), p.465-472 |
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| creator | Han, Dong Wook Tapia, Natalia Hermann, Andreas Hemmer, Kathrin Höing, Susanne Araúzo-Bravo, Marcos J. Zaehres, Holm Wu, Guangming Frank, Stefan Moritz, Sören Greber, Boris Yang, Ji Hun Lee, Hoon Taek Schwamborn, Jens C. Storch, Alexander Schöler, Hans R. |
| description | 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.
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► Direct reprogramming of differentiated cells into self-renewing somatic stem cells ► Set of four transcription factors induces neural stem cell program in fibroblasts ► Reprogramming without risk of teratomas ► Induced neural stem cells behave as their endogenous counterparts |
| doi_str_mv | 10.1016/j.stem.2012.02.021 |
| format | Article |
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► Direct reprogramming of differentiated cells into self-renewing somatic stem cells ► Set of four transcription factors induces neural stem cell program in fibroblasts ► Reprogramming without risk of teratomas ► Induced neural stem cells behave as their endogenous counterparts</description><identifier>ISSN: 1934-5909</identifier><identifier>EISSN: 1875-9777</identifier><identifier>DOI: 10.1016/j.stem.2012.02.021</identifier><identifier>PMID: 22445517</identifier><language>eng</language><publisher>Cambridge, MA: Elsevier Inc</publisher><subject>Animals ; Antigens, Differentiation - biosynthesis ; Antigens, Differentiation - genetics ; Biological and medical sciences ; Cell Dedifferentiation ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation - genetics ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Mice ; Molecular and cellular biology ; Neural Stem Cells - cytology ; Neural Stem Cells - metabolism ; Transcription Factors - biosynthesis ; Transcription Factors - genetics</subject><ispartof>Cell stem cell, 2012-04, Vol.10 (4), p.465-472</ispartof><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-222364658451b6c15bf6dec5932e393eb97900bc64c899cb7992c09ef70203173</citedby><cites>FETCH-LOGICAL-c462t-222364658451b6c15bf6dec5932e393eb97900bc64c899cb7992c09ef70203173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1934590912001142$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25812511$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22445517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Dong Wook</creatorcontrib><creatorcontrib>Tapia, Natalia</creatorcontrib><creatorcontrib>Hermann, Andreas</creatorcontrib><creatorcontrib>Hemmer, Kathrin</creatorcontrib><creatorcontrib>Höing, Susanne</creatorcontrib><creatorcontrib>Araúzo-Bravo, Marcos J.</creatorcontrib><creatorcontrib>Zaehres, Holm</creatorcontrib><creatorcontrib>Wu, Guangming</creatorcontrib><creatorcontrib>Frank, Stefan</creatorcontrib><creatorcontrib>Moritz, Sören</creatorcontrib><creatorcontrib>Greber, Boris</creatorcontrib><creatorcontrib>Yang, Ji Hun</creatorcontrib><creatorcontrib>Lee, Hoon Taek</creatorcontrib><creatorcontrib>Schwamborn, Jens C.</creatorcontrib><creatorcontrib>Storch, Alexander</creatorcontrib><creatorcontrib>Schöler, Hans R.</creatorcontrib><title>Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors</title><title>Cell stem cell</title><addtitle>Cell Stem Cell</addtitle><description>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.
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► Direct reprogramming of differentiated cells into self-renewing somatic stem cells ► Set of four transcription factors induces neural stem cell program in fibroblasts ► Reprogramming without risk of teratomas ► Induced neural stem cells behave as their endogenous counterparts</description><subject>Animals</subject><subject>Antigens, Differentiation - biosynthesis</subject><subject>Antigens, Differentiation - genetics</subject><subject>Biological and medical sciences</subject><subject>Cell Dedifferentiation</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation - genetics</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Neural Stem Cells - cytology</subject><subject>Neural Stem Cells - metabolism</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><issn>1934-5909</issn><issn>1875-9777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1LXDEUhkNpqdb6B1yUbIrd3DEnNx8TcCNjpxVsC21dhyT3XMlwPzS5I_jvze2MdSccSBbPefPyhJATYAtgoM42izxhv-AM-ILNA2_IISy1rIzW-m25m1pU0jBzQD7kvGFMamD6PTngXAgpQR-SH5cxYZjob7xL421yfR-HWzq2dB19Gn3n8pRpHKaR_sRtch39U56kK-y6TP0jvcQ2DtjQtQvTmPJH8q51Xcbj_XlEbtZf_66-V9e_vl2tLq6rIBSfKs55rYSSSyHBqwDSt6rBIE3NsTY1eqMNYz4oEZbGBK-N4YEZbDXjrAZdH5HTXW4pfb_FPNk-5lBKuQHHbbbG1MUQ56qQX14lCwYcpABRUL5DQxpzTtjauxR7lx4LNHPKbuws3M7CLZsHytKnff7W99j8X3k2XIDPe8Dl4Lo2uSHE_MLJJXAJc9D5jsPi7SFisjlEHAI2_z7INmN8rccTU7ecMw</recordid><startdate>20120406</startdate><enddate>20120406</enddate><creator>Han, Dong Wook</creator><creator>Tapia, Natalia</creator><creator>Hermann, Andreas</creator><creator>Hemmer, Kathrin</creator><creator>Höing, Susanne</creator><creator>Araúzo-Bravo, Marcos J.</creator><creator>Zaehres, Holm</creator><creator>Wu, Guangming</creator><creator>Frank, Stefan</creator><creator>Moritz, Sören</creator><creator>Greber, Boris</creator><creator>Yang, Ji Hun</creator><creator>Lee, Hoon Taek</creator><creator>Schwamborn, Jens C.</creator><creator>Storch, Alexander</creator><creator>Schöler, Hans R.</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20120406</creationdate><title>Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors</title><author>Han, Dong Wook ; Tapia, Natalia ; Hermann, Andreas ; Hemmer, Kathrin ; Höing, Susanne ; Araúzo-Bravo, Marcos J. ; Zaehres, Holm ; Wu, Guangming ; Frank, Stefan ; Moritz, Sören ; Greber, Boris ; Yang, Ji Hun ; Lee, Hoon Taek ; Schwamborn, Jens C. ; Storch, Alexander ; Schöler, Hans R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-222364658451b6c15bf6dec5932e393eb97900bc64c899cb7992c09ef70203173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antigens, Differentiation - biosynthesis</topic><topic>Antigens, Differentiation - genetics</topic><topic>Biological and medical sciences</topic><topic>Cell Dedifferentiation</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation - genetics</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Neural Stem Cells - cytology</topic><topic>Neural Stem Cells - metabolism</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Dong Wook</creatorcontrib><creatorcontrib>Tapia, Natalia</creatorcontrib><creatorcontrib>Hermann, Andreas</creatorcontrib><creatorcontrib>Hemmer, Kathrin</creatorcontrib><creatorcontrib>Höing, Susanne</creatorcontrib><creatorcontrib>Araúzo-Bravo, Marcos J.</creatorcontrib><creatorcontrib>Zaehres, Holm</creatorcontrib><creatorcontrib>Wu, Guangming</creatorcontrib><creatorcontrib>Frank, Stefan</creatorcontrib><creatorcontrib>Moritz, Sören</creatorcontrib><creatorcontrib>Greber, Boris</creatorcontrib><creatorcontrib>Yang, Ji Hun</creatorcontrib><creatorcontrib>Lee, Hoon Taek</creatorcontrib><creatorcontrib>Schwamborn, Jens C.</creatorcontrib><creatorcontrib>Storch, Alexander</creatorcontrib><creatorcontrib>Schöler, Hans R.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell stem cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Dong Wook</au><au>Tapia, Natalia</au><au>Hermann, Andreas</au><au>Hemmer, Kathrin</au><au>Höing, Susanne</au><au>Araúzo-Bravo, Marcos J.</au><au>Zaehres, Holm</au><au>Wu, Guangming</au><au>Frank, Stefan</au><au>Moritz, Sören</au><au>Greber, Boris</au><au>Yang, Ji Hun</au><au>Lee, Hoon Taek</au><au>Schwamborn, Jens C.</au><au>Storch, Alexander</au><au>Schöler, Hans R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors</atitle><jtitle>Cell stem cell</jtitle><addtitle>Cell Stem Cell</addtitle><date>2012-04-06</date><risdate>2012</risdate><volume>10</volume><issue>4</issue><spage>465</spage><epage>472</epage><pages>465-472</pages><issn>1934-5909</issn><eissn>1875-9777</eissn><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.
[Display omitted]
► Direct reprogramming of differentiated cells into self-renewing somatic stem cells ► Set of four transcription factors induces neural stem cell program in fibroblasts ► Reprogramming without risk of teratomas ► Induced neural stem cells behave as their endogenous counterparts</abstract><cop>Cambridge, MA</cop><pub>Elsevier Inc</pub><pmid>22445517</pmid><doi>10.1016/j.stem.2012.02.021</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Antigens, Differentiation - biosynthesis Antigens, Differentiation - genetics Biological and medical sciences Cell Dedifferentiation Cell differentiation, maturation, development, hematopoiesis Cell physiology Fibroblasts - cytology Fibroblasts - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Regulation - genetics Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Mice Molecular and cellular biology Neural Stem Cells - cytology Neural Stem Cells - metabolism Transcription Factors - biosynthesis Transcription Factors - genetics |
| title | Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors |
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