Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1.

Autor:	Tejwani L; Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: leon.tejwani@yale.edu., Ravindra NG; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Computer Science, Yale University, New Haven, CT 06510, USA., Lee C; Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., Cheng Y; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA., Nguyen B; University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA., Luttik K; Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., Ni L; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA., Zhang S; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA., Morrison LM; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA., Gionco J; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA., Xiang Y; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06510, USA., Yoon J; Yale College, New Haven, CT 06510, USA., Ro H; Yale College, New Haven, CT 06510, USA., Haidery F; Yale College, New Haven, CT 06510, USA., Grijalva RM; Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., Bae E; Yale College, New Haven, CT 06510, USA., Kim K; Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA; Department of Psychiatry, Yale School of Medicine, New Haven, CT 06510, USA., Martuscello RT; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA., Orr HT; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA., Zoghbi HY; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA., McLoughlin HS; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Ranum LPW; Department of Molecular Genetics and Microbiology, Center for Neurogenetics, College of Medicine, Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA., Shakkottai VG; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Faust PL; Department of Pathology and Cell Biology, Columbia University Irving Medical Center and the New York Presbyterian Hospital, New York, NY 10032, USA., Wang S; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: siyuan.wang@yale.edu., van Dijk D; Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA; Department of Computer Science, Yale University, New Haven, CT 06510, USA. Electronic address: david.vandijk@yale.edu., Lim J; Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06510, USA; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06510, USA; Wu Tsai Institute, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: janghoo.lim@yale.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2024 Feb 07; Vol. 112 (3), pp. 362-383.e15. Date of Electronic Publication: 2023 Nov 27.
DOI:	10.1016/j.neuron.2023.10.039
Abstrakt:	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. Competing Interests: Declaration of interests S.W. is an inventor on a patent applied for by Harvard University related to MERFISH and a consultant and shareholder of Translura, Inc. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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