Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
Neurodegeneration is a protracted process involving progressive changes in myriad cell types that ultimately results in the death of vulnerable neuronal populations. To dissect how individual cell types within a heterogeneous tissue contribute to the pathogenesis and progression of a neurodegenerative disorder, we performed longitudinal single-nucleus RNA sequencing of mouse and human spinocerebellar ataxia type 1 (SCA1) cerebellar tissue, establishing continuous dynamic trajectories of each cell population. Importantly, we defined the precise transcriptional changes that precede loss of Purkinje cells and, for the first time, identified robust early transcriptional dysregulation in unipolar brush cells and oligodendroglia. Finally, we applied a deep learning method to predict disease state accurately and identified specific features that enable accurate distinction of wild-type and SCA1 cells. Together, this work reveals new roles for diverse cerebellar cell types in SCA1 and provides a generalizable analysis framework for studying neurodegeneration.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:112 |
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| Enthalten in: |
Neuron - 112(2024), 3 vom: 07. Feb., Seite 362-383.e15 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tejwani, Leon [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 19.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neuron.2023.10.039 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Neurodegeneration is a protracted process involving progressive changes in myriad cell types that ultimately results in the death of vulnerable neuronal populations. To dissect how individual cell types within a heterogeneous tissue contribute to the pathogenesis and progression of a neurodegenerative disorder, we performed longitudinal single-nucleus RNA sequencing of mouse and human spinocerebellar ataxia type 1 (SCA1) cerebellar tissue, establishing continuous dynamic trajectories of each cell population. Importantly, we defined the precise transcriptional changes that precede loss of Purkinje cells and, for the first time, identified robust early transcriptional dysregulation in unipolar brush cells and oligodendroglia. Finally, we applied a deep learning method to predict disease state accurately and identified specific features that enable accurate distinction of wild-type and SCA1 cells. Together, this work reveals new roles for diverse cerebellar cell types in SCA1 and provides a generalizable analysis framework for studying neurodegeneration | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Purkinje cell | |
| 650 | 4 | |a SCA1 | |
| 650 | 4 | |a ataxin-1 | |
| 650 | 4 | |a machine learning | |
| 650 | 4 | |a neurodegeneration | |
| 650 | 4 | |a oligodendrocyte | |
| 650 | 4 | |a oligodendrocyte progenitor cell | |
| 650 | 4 | |a single-nucleus RNA sequencing | |
| 650 | 4 | |a spinocerebellar ataxia type 1 | |
| 650 | 4 | |a unipolar brush cells | |
| 650 | 7 | |a Ataxin-1 |2 NLM | |
| 700 | 1 | |a Ravindra, Neal G |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Changwoo |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Yubao |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Billy |e verfasserin |4 aut | |
| 700 | 1 | |a Luttik, Kimberly |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Luhan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shupei |e verfasserin |4 aut | |
| 700 | 1 | |a Morrison, Logan M |e verfasserin |4 aut | |
| 700 | 1 | |a Gionco, John |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Yangfei |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Ro, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Haidery, Fatema |e verfasserin |4 aut | |
| 700 | 1 | |a Grijalva, Rosalie M |e verfasserin |4 aut | |
| 700 | 1 | |a Bae, Eunwoo |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kristen |e verfasserin |4 aut | |
| 700 | 1 | |a Martuscello, Regina T |e verfasserin |4 aut | |
| 700 | 1 | |a Orr, Harry T |e verfasserin |4 aut | |
| 700 | 1 | |a Zoghbi, Huda Y |e verfasserin |4 aut | |
| 700 | 1 | |a McLoughlin, Hayley S |e verfasserin |4 aut | |
| 700 | 1 | |a Ranum, Laura P W |e verfasserin |4 aut | |
| 700 | 1 | |a Shakkottai, Vikram G |e verfasserin |4 aut | |
| 700 | 1 | |a Faust, Phyllis L |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Siyuan |e verfasserin |4 aut | |
| 700 | 1 | |a van Dijk, David |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Janghoo |e verfasserin |4 aut | |
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