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CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion
Astrocyte-to-neuron conversion is a promising avenue for neuronal replacement therapy. Neurons are particularly dependent on mitochondrial function, but how well mitochondria adapt to the new fate is unknown. Here, we determined the comprehensive mitochondrial proteome of cortical astrocytes and neu...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939544/ https://www.ncbi.nlm.nih.gov/pubmed/33202244 http://dx.doi.org/10.1016/j.stem.2020.10.015 |
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author | Russo, Gianluca L. Sonsalla, Giovanna Natarajan, Poornemaa Breunig, Christopher T. Bulli, Giorgia Merl-Pham, Juliane Schmitt, Sabine Giehrl-Schwab, Jessica Giesert, Florian Jastroch, Martin Zischka, Hans Wurst, Wolfgang Stricker, Stefan H. Hauck, Stefanie M. Masserdotti, Giacomo Götz, Magdalena |
author_facet | Russo, Gianluca L. Sonsalla, Giovanna Natarajan, Poornemaa Breunig, Christopher T. Bulli, Giorgia Merl-Pham, Juliane Schmitt, Sabine Giehrl-Schwab, Jessica Giesert, Florian Jastroch, Martin Zischka, Hans Wurst, Wolfgang Stricker, Stefan H. Hauck, Stefanie M. Masserdotti, Giacomo Götz, Magdalena |
author_sort | Russo, Gianluca L. |
collection | PubMed |
description | Astrocyte-to-neuron conversion is a promising avenue for neuronal replacement therapy. Neurons are particularly dependent on mitochondrial function, but how well mitochondria adapt to the new fate is unknown. Here, we determined the comprehensive mitochondrial proteome of cortical astrocytes and neurons, identifying about 150 significantly enriched mitochondrial proteins for each cell type, including transporters, metabolic enzymes, and cell-type-specific antioxidants. Monitoring their transition during reprogramming revealed late and only partial adaptation to the neuronal identity. Early dCas9-mediated activation of genes encoding mitochondrial proteins significantly improved conversion efficiency, particularly for neuron-enriched but not astrocyte-enriched antioxidant proteins. For example, Sod1 not only improves the survival of the converted neurons but also elicits a faster conversion pace, indicating that mitochondrial proteins act as enablers and drivers in this process. Transcriptional engineering of mitochondrial proteins with other functions improved reprogramming as well, demonstrating a broader role of mitochondrial proteins during fate conversion. |
format | Online Article Text |
id | pubmed-7939544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-79395442021-03-16 CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion Russo, Gianluca L. Sonsalla, Giovanna Natarajan, Poornemaa Breunig, Christopher T. Bulli, Giorgia Merl-Pham, Juliane Schmitt, Sabine Giehrl-Schwab, Jessica Giesert, Florian Jastroch, Martin Zischka, Hans Wurst, Wolfgang Stricker, Stefan H. Hauck, Stefanie M. Masserdotti, Giacomo Götz, Magdalena Cell Stem Cell Short Article Astrocyte-to-neuron conversion is a promising avenue for neuronal replacement therapy. Neurons are particularly dependent on mitochondrial function, but how well mitochondria adapt to the new fate is unknown. Here, we determined the comprehensive mitochondrial proteome of cortical astrocytes and neurons, identifying about 150 significantly enriched mitochondrial proteins for each cell type, including transporters, metabolic enzymes, and cell-type-specific antioxidants. Monitoring their transition during reprogramming revealed late and only partial adaptation to the neuronal identity. Early dCas9-mediated activation of genes encoding mitochondrial proteins significantly improved conversion efficiency, particularly for neuron-enriched but not astrocyte-enriched antioxidant proteins. For example, Sod1 not only improves the survival of the converted neurons but also elicits a faster conversion pace, indicating that mitochondrial proteins act as enablers and drivers in this process. Transcriptional engineering of mitochondrial proteins with other functions improved reprogramming as well, demonstrating a broader role of mitochondrial proteins during fate conversion. Cell Press 2021-03-04 /pmc/articles/PMC7939544/ /pubmed/33202244 http://dx.doi.org/10.1016/j.stem.2020.10.015 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Short Article Russo, Gianluca L. Sonsalla, Giovanna Natarajan, Poornemaa Breunig, Christopher T. Bulli, Giorgia Merl-Pham, Juliane Schmitt, Sabine Giehrl-Schwab, Jessica Giesert, Florian Jastroch, Martin Zischka, Hans Wurst, Wolfgang Stricker, Stefan H. Hauck, Stefanie M. Masserdotti, Giacomo Götz, Magdalena CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion |
title | CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion |
title_full | CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion |
title_fullStr | CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion |
title_full_unstemmed | CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion |
title_short | CRISPR-Mediated Induction of Neuron-Enriched Mitochondrial Proteins Boosts Direct Glia-to-Neuron Conversion |
title_sort | crispr-mediated induction of neuron-enriched mitochondrial proteins boosts direct glia-to-neuron conversion |
topic | Short Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939544/ https://www.ncbi.nlm.nih.gov/pubmed/33202244 http://dx.doi.org/10.1016/j.stem.2020.10.015 |
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