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Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion

Ectopic expression of a single neural transcription factor NeuroD1 can reprogram reactive glial cells into functional neurons both in vitro and in vivo, but the underlying mechanisms are not well understood yet. Here, we used RNA‐sequencing technology to capture the transcriptomic changes at differe...

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Autores principales: Ma, Ning‐Xin, Puls, Brendan, Chen, Gong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540770/
https://www.ncbi.nlm.nih.gov/pubmed/35606902
http://dx.doi.org/10.1002/dneu.22882
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author Ma, Ning‐Xin
Puls, Brendan
Chen, Gong
author_facet Ma, Ning‐Xin
Puls, Brendan
Chen, Gong
author_sort Ma, Ning‐Xin
collection PubMed
description Ectopic expression of a single neural transcription factor NeuroD1 can reprogram reactive glial cells into functional neurons both in vitro and in vivo, but the underlying mechanisms are not well understood yet. Here, we used RNA‐sequencing technology to capture the transcriptomic changes at different time points during the reprogramming process. We found that following NeuroD1 overexpression, astroglial genes (ACTG1, ALDH1A3, EMP1, CLDN6, SOX21) were significantly downregulated, whereas neuronal genes (DCX, RBFOX3/NeuN, CUX2, RELN, SNAP25) were significantly upregulated. NeuroD family members (NeuroD1/2/6) and signaling pathways (Wnt, MAPK, cAMP) as well as neurotransmitter receptors (acetylcholine, somatostatin, dopamine) were also significantly upregulated. Gene co‐expression analysis identified many central genes among the NeuroD1‐interacting network, including CABP7, KIAA1456, SSTR2, GADD45G, LRRTM2, and INSM1. Compared to chemical conversion, we found that NeuroD1 acted as a strong driving force and triggered fast transcriptomic changes during astrocyte‐to‐neuron conversion process. Together, this study reveals many important downstream targets of NeuroD1 such as HES6, BHLHE22, INSM1, CHRNA1/3, CABP7, and SSTR2, which may play critical roles during the transcriptomic landscape shift from a glial profile to a neuronal profile.
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spelling pubmed-95407702022-10-14 Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion Ma, Ning‐Xin Puls, Brendan Chen, Gong Dev Neurobiol Research Articles Ectopic expression of a single neural transcription factor NeuroD1 can reprogram reactive glial cells into functional neurons both in vitro and in vivo, but the underlying mechanisms are not well understood yet. Here, we used RNA‐sequencing technology to capture the transcriptomic changes at different time points during the reprogramming process. We found that following NeuroD1 overexpression, astroglial genes (ACTG1, ALDH1A3, EMP1, CLDN6, SOX21) were significantly downregulated, whereas neuronal genes (DCX, RBFOX3/NeuN, CUX2, RELN, SNAP25) were significantly upregulated. NeuroD family members (NeuroD1/2/6) and signaling pathways (Wnt, MAPK, cAMP) as well as neurotransmitter receptors (acetylcholine, somatostatin, dopamine) were also significantly upregulated. Gene co‐expression analysis identified many central genes among the NeuroD1‐interacting network, including CABP7, KIAA1456, SSTR2, GADD45G, LRRTM2, and INSM1. Compared to chemical conversion, we found that NeuroD1 acted as a strong driving force and triggered fast transcriptomic changes during astrocyte‐to‐neuron conversion process. Together, this study reveals many important downstream targets of NeuroD1 such as HES6, BHLHE22, INSM1, CHRNA1/3, CABP7, and SSTR2, which may play critical roles during the transcriptomic landscape shift from a glial profile to a neuronal profile. John Wiley and Sons Inc. 2022-05-23 2022 /pmc/articles/PMC9540770/ /pubmed/35606902 http://dx.doi.org/10.1002/dneu.22882 Text en © 2022 The Authors. Developmental Neurobiology published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Ma, Ning‐Xin
Puls, Brendan
Chen, Gong
Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion
title Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion
title_full Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion
title_fullStr Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion
title_full_unstemmed Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion
title_short Transcriptomic analyses of NeuroD1‐mediated astrocyte‐to‐neuron conversion
title_sort transcriptomic analyses of neurod1‐mediated astrocyte‐to‐neuron conversion
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540770/
https://www.ncbi.nlm.nih.gov/pubmed/35606902
http://dx.doi.org/10.1002/dneu.22882
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