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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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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. |
format | Online Article Text |
id | pubmed-9540770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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