Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1

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...

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Main Authors: Chanda, Soham, Ang, Cheen Euong, Davila, Jonathan, Pak, ChangHui, Mall, Moritz, Lee, Qian Yi, Ahlenius, Henrik, Jung, Seung Woo, Südhof, Thomas C., Wernig, Marius
Format: Online
Language:English
Published: Elsevier 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176533/
id pubmed-4176533
recordtype oai_dc
spelling pubmed-41765332014-09-30 Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1 Chanda, Soham Ang, Cheen Euong Davila, Jonathan Pak, ChangHui Mall, Moritz Lee, Qian Yi Ahlenius, Henrik Jung, Seung Woo Südhof, Thomas C. Wernig, Marius Article 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. Elsevier 2014-07-04 /pmc/articles/PMC4176533/ /pubmed/25254342 http://dx.doi.org/10.1016/j.stemcr.2014.05.020 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Chanda, Soham
Ang, Cheen Euong
Davila, Jonathan
Pak, ChangHui
Mall, Moritz
Lee, Qian Yi
Ahlenius, Henrik
Jung, Seung Woo
Südhof, Thomas C.
Wernig, Marius
spellingShingle Chanda, Soham
Ang, Cheen Euong
Davila, Jonathan
Pak, ChangHui
Mall, Moritz
Lee, Qian Yi
Ahlenius, Henrik
Jung, Seung Woo
Südhof, Thomas C.
Wernig, Marius
Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1
author_facet Chanda, Soham
Ang, Cheen Euong
Davila, Jonathan
Pak, ChangHui
Mall, Moritz
Lee, Qian Yi
Ahlenius, Henrik
Jung, Seung Woo
Südhof, Thomas C.
Wernig, Marius
author_sort Chanda, Soham
title 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_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_sort generation of induced neuronal cells by the single reprogramming factor ascl1
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.
publisher Elsevier
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176533/
_version_ 1613137813458386944

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