Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle
Abstract Stem cells show intrinsic interferon signalling, which protects them from viral infections at all ages. In the ageing brain, interferon signalling also reduces the ability of stem cells to activate. Whether these functions are linked and at what time interferons start taking on a role in st...
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-01-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202216434 |
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| author | Damian Carvajal Ibañez Maxim Skabkin Jooa Hooli Santiago Cerrizuela Manuel Göpferich Adrien Jolly Katrin Volk Marc Zumwinkel Matilde Bertolini Gianluca Figlia Thomas Höfer Guenter Kramer Simon Anders Aurelio A Teleman Anna Marciniak‐Czochra Ana Martin‐Villalba |
| author_facet | Damian Carvajal Ibañez Maxim Skabkin Jooa Hooli Santiago Cerrizuela Manuel Göpferich Adrien Jolly Katrin Volk Marc Zumwinkel Matilde Bertolini Gianluca Figlia Thomas Höfer Guenter Kramer Simon Anders Aurelio A Teleman Anna Marciniak‐Czochra Ana Martin‐Villalba |
| author_sort | Damian Carvajal Ibañez |
| collection | DOAJ |
| description | Abstract Stem cells show intrinsic interferon signalling, which protects them from viral infections at all ages. In the ageing brain, interferon signalling also reduces the ability of stem cells to activate. Whether these functions are linked and at what time interferons start taking on a role in stem cell functioning is unknown. Additionally, the molecular link between interferons and activation in neural stem cells and how this relates to progenitor production is not well understood. Here we combine single‐cell transcriptomics, RiboSeq and mathematical models of interferon to show that this pathway is important for proper stem cell function at all ages in mice. Interferon orchestrates cell cycle and mTOR activity to post‐transcriptionally repress Sox2 and induces quiescence. The interferon response then decreases in the subsequent maturation states. Mathematical simulations indicate that this regulation is beneficial for the young and harmful for the old brain. Our study establishes molecular mechanisms of interferon in stem cells and interferons as genuine regulators of stem cell homeostasis and a potential therapeutic target to repair the ageing brain. |
| format | Article |
| id | doaj-art-c039cae925bd4fe8acd4f4d3519e3e36 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-c039cae925bd4fe8acd4f4d3519e3e362025-08-20T03:46:28ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-01-0115411810.15252/emmm.202216434Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycleDamian Carvajal Ibañez0Maxim Skabkin1Jooa Hooli2Santiago Cerrizuela3Manuel Göpferich4Adrien Jolly5Katrin Volk6Marc Zumwinkel7Matilde Bertolini8Gianluca Figlia9Thomas Höfer10Guenter Kramer11Simon Anders12Aurelio A Teleman13Anna Marciniak‐Czochra14Ana Martin‐Villalba15Division of Molecular Neurobiology, German Cancer Research Center (DKFZ)Division of Molecular Neurobiology, German Cancer Research Center (DKFZ)Division of Molecular Neurobiology, German Cancer Research Center (DKFZ)Division of Molecular Neurobiology, German Cancer Research Center (DKFZ)Division of Molecular Neurobiology, German Cancer Research Center (DKFZ)Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ)Division of Molecular Neurobiology, German Cancer Research Center (DKFZ)Division of Molecular Neurobiology, German Cancer Research Center (DKFZ)Center for Molecular Biology of Heidelberg University (ZMBH) & German Cancer Research Center (DKFZ), DKFZ‐ZMBH AllianceFaculty of Biosciences, Heidelberg UniversityDivision of Theoretical Systems Biology, German Cancer Research Center (DKFZ)Center for Molecular Biology of Heidelberg University (ZMBH) & German Cancer Research Center (DKFZ), DKFZ‐ZMBH AllianceBioquant, Heidelberg UniversityDivision of Signal Transduction in Cancer and Metabolism, German Cancer Research Center (DKFZ)Institute of Applied Mathematics, Heidelberg UniversityDivision of Molecular Neurobiology, German Cancer Research Center (DKFZ)Abstract Stem cells show intrinsic interferon signalling, which protects them from viral infections at all ages. In the ageing brain, interferon signalling also reduces the ability of stem cells to activate. Whether these functions are linked and at what time interferons start taking on a role in stem cell functioning is unknown. Additionally, the molecular link between interferons and activation in neural stem cells and how this relates to progenitor production is not well understood. Here we combine single‐cell transcriptomics, RiboSeq and mathematical models of interferon to show that this pathway is important for proper stem cell function at all ages in mice. Interferon orchestrates cell cycle and mTOR activity to post‐transcriptionally repress Sox2 and induces quiescence. The interferon response then decreases in the subsequent maturation states. Mathematical simulations indicate that this regulation is beneficial for the young and harmful for the old brain. Our study establishes molecular mechanisms of interferon in stem cells and interferons as genuine regulators of stem cell homeostasis and a potential therapeutic target to repair the ageing brain.https://doi.org/10.15252/emmm.202216434ageingdormancyinterferonmTORstem cells |
| spellingShingle | Damian Carvajal Ibañez Maxim Skabkin Jooa Hooli Santiago Cerrizuela Manuel Göpferich Adrien Jolly Katrin Volk Marc Zumwinkel Matilde Bertolini Gianluca Figlia Thomas Höfer Guenter Kramer Simon Anders Aurelio A Teleman Anna Marciniak‐Czochra Ana Martin‐Villalba Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle EMBO Molecular Medicine ageing dormancy interferon mTOR stem cells |
| title | Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle |
| title_full | Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle |
| title_fullStr | Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle |
| title_full_unstemmed | Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle |
| title_short | Interferon regulates neural stem cell function at all ages by orchestrating mTOR and cell cycle |
| title_sort | interferon regulates neural stem cell function at all ages by orchestrating mtor and cell cycle |
| topic | ageing dormancy interferon mTOR stem cells |
| url | https://doi.org/10.15252/emmm.202216434 |
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