Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1
Direct conversion of nonneural cells to functional neurons holds great promise for neurological disease modeling and regenerative medicine. We previously reported rapid reprogramming of mouse embryonic fibroblasts (MEFs) into mature induced neuronal (iN) cells by forced expression of three transcrip...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-08-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671114001878 |
| _version_ | 1811270218880647168 |
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| author | Soham Chanda Cheen Euong Ang Jonathan Davila ChangHui Pak Moritz Mall Qian Yi Lee Henrik Ahlenius Seung Woo Jung Thomas C. Südhof Marius Wernig |
| author_facet | Soham Chanda Cheen Euong Ang Jonathan Davila ChangHui Pak Moritz Mall Qian Yi Lee Henrik Ahlenius Seung Woo Jung Thomas C. Südhof Marius Wernig |
| author_sort | Soham Chanda |
| collection | DOAJ |
| description | Direct conversion of nonneural cells to functional neurons holds great promise for neurological disease modeling and regenerative medicine. We previously reported rapid reprogramming of mouse embryonic fibroblasts (MEFs) into mature induced neuronal (iN) cells by forced expression of three transcription factors: ASCL1, MYT1L, and BRN2. Here, we show that ASCL1 alone is sufficient to generate functional iN cells from mouse and human fibroblasts and embryonic stem cells, indicating that ASCL1 is the key driver of iN cell reprogramming in different cell contexts and that the role of MYT1L and BRN2 is primarily to enhance the neuronal maturation process. ASCL1-induced single-factor neurons (1F-iN) expressed mature neuronal markers, exhibited typical passive and active intrinsic membrane properties, and formed functional pre- and postsynaptic structures. Surprisingly, ASCL1-induced iN cells were predominantly excitatory, demonstrating that ASCL1 is permissive but alone not deterministic for the inhibitory neuronal lineage. |
| first_indexed | 2024-04-12T21:56:57Z |
| format | Article |
| id | doaj.art-0b12c0647c8849d4aed6bb170936af84 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-12T21:56:57Z |
| publishDate | 2014-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-0b12c0647c8849d4aed6bb170936af842022-12-22T03:15:17ZengElsevierStem Cell Reports2213-67112014-08-013228229610.1016/j.stemcr.2014.05.020Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1Soham Chanda0Cheen Euong Ang1Jonathan Davila2ChangHui Pak3Moritz Mall4Qian Yi Lee5Henrik Ahlenius6Seung Woo Jung7Thomas C. Südhof8Marius Wernig9Institute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University, Stanford, CA 94305, USAInstitute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University, Stanford, CA 94305, USAInstitute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University, Stanford, CA 94305, USADepartment of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USAInstitute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University, Stanford, CA 94305, USAInstitute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University, Stanford, CA 94305, USAInstitute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University, Stanford, CA 94305, USAInstitute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University, Stanford, CA 94305, USADepartment of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USAInstitute for Stem Cell Biology and Regenerative Medicine and Department of Pathology, Stanford University, Stanford, CA 94305, USADirect conversion of nonneural cells to functional neurons holds great promise for neurological disease modeling and regenerative medicine. We previously reported rapid reprogramming of mouse embryonic fibroblasts (MEFs) into mature induced neuronal (iN) cells by forced expression of three transcription factors: ASCL1, MYT1L, and BRN2. Here, we show that ASCL1 alone is sufficient to generate functional iN cells from mouse and human fibroblasts and embryonic stem cells, indicating that ASCL1 is the key driver of iN cell reprogramming in different cell contexts and that the role of MYT1L and BRN2 is primarily to enhance the neuronal maturation process. ASCL1-induced single-factor neurons (1F-iN) expressed mature neuronal markers, exhibited typical passive and active intrinsic membrane properties, and formed functional pre- and postsynaptic structures. Surprisingly, ASCL1-induced iN cells were predominantly excitatory, demonstrating that ASCL1 is permissive but alone not deterministic for the inhibitory neuronal lineage.http://www.sciencedirect.com/science/article/pii/S2213671114001878 |
| spellingShingle | Soham Chanda Cheen Euong Ang Jonathan Davila ChangHui Pak Moritz Mall Qian Yi Lee Henrik Ahlenius Seung Woo Jung Thomas C. Südhof Marius Wernig Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1 Stem Cell Reports |
| title | Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1 |
| title_full | Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1 |
| title_fullStr | Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1 |
| title_full_unstemmed | Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1 |
| title_short | Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1 |
| title_sort | generation of induced neuronal cells by the single reprogramming factor ascl1 |
| url | http://www.sciencedirect.com/science/article/pii/S2213671114001878 |
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