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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 LU ; Jung, Seung Woo ; Südhof, Thomas C. and Wernig, Marius (2014) In Stem Cell Reports 3(2). p.282-296
Abstract

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,... (More)

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.

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author
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publishing date
type
Contribution to journal
publication status
published
in
Stem Cell Reports
volume
3
issue
2
pages
282 - 296
publisher
Cell Press
external identifiers
  • scopus:84924219718
  • pmid:25254342
ISSN
2213-6711
DOI
10.1016/j.stemcr.2014.05.020
language
English
LU publication?
no
id
07268ef1-b771-40ae-b9b9-ab963a842a6b
date added to LUP
2025-08-26 11:22:41
date last changed
2025-09-09 12:23:03
@article{07268ef1-b771-40ae-b9b9-ab963a842a6b,
  abstract     = {{<p>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.</p>}},
  author       = {{Chanda, Soham and Ang, Cheen Euong and Davila, Jonathan and Pak, Changhui and Mall, Moritz and Lee, Qian Yi and Ahlenius, Henrik and Jung, Seung Woo and Südhof, Thomas C. and Wernig, Marius}},
  issn         = {{2213-6711}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{2}},
  pages        = {{282--296}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Generation of induced neuronal cells by the single reprogramming factor ASCL1}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2014.05.020}},
  doi          = {{10.1016/j.stemcr.2014.05.020}},
  volume       = {{3}},
  year         = {{2014}},
}