Decoding hereditary spastic paraplegia pathogenicity through transcriptomic profiling

Nicolas James Ho; Xiao Chen; Yong Lei; Shen Gu

doi:10.24272/j.issn.2095-8137.2022.281

Volume 44 Issue 3

May 2023

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Nicolas James Ho, Xiao Chen, Yong Lei, Shen Gu. Decoding hereditary spastic paraplegia pathogenicity through transcriptomic profiling. Zoological Research, 2023, 44(3): 650-662. doi: 10.24272/j.issn.2095-8137.2022.281

Citation:

Nicolas James Ho, Xiao Chen, Yong Lei, Shen Gu. Decoding hereditary spastic paraplegia pathogenicity through transcriptomic profiling. Zoological Research, 2023, 44(3): 650-662. doi: 10.24272/j.issn.2095-8137.2022.281

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Decoding hereditary spastic paraplegia pathogenicity through transcriptomic profiling

doi: 10.24272/j.issn.2095-8137.2022.281

Nicolas James Ho¹,
Xiao Chen^{2, 3, 4, 5, 6},
Yong Lei^{7, 8
,
,},
Shen Gu^{1, 9, 10, 11
,
,}

1.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
2.
Dr. Li Dak Sum-Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
3.
Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
4.
Zhejiang University-University of Edinburgh Institute & School of Basic Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
5.
Department of Sports Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
6.
China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, Zhejiang, 310058 China
7.
School of Medicine, The Chinese University of Hong Kong (Shenzhen), Shenzhen, Guangdong 518172, China
8.
The Chinese University of Hong Kong (Shenzhen), Shenzhen Futian Biomedical Innovation R&D Center, Shenzhen, Guangdong 518172, China
9.
Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
10.
Kunming Institute of Zoology Chinese Academy of Sciences, The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Hong Kong SAR, China
11.
Hong Kong Branch of CAS Center for Excellence in Animal Evolution and Genetics, The Chinese University of Hong Kong, Hong Kong SAR, China

Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
N.J.H. acquired, analyzed, and interpreted the data. N.J.H. and S.G. designed the study and wrote the manuscript. X.C. and Y.L. conceived, critically revised, and supervised the work. All authors read and approved the final version of the manuscript.

Funds: This study was supported by the General Research Fund from the Research Grants Council of Hong Kong (24101921), Direct Grant from the Chinese University of Hong Kong (2020.096), National Natural Science Foundation of China (32170583, 82202045), Hong Kong RGC-CRF Equipment Fund C5033-19E, Shenzhen-Hong Kong Cooperation Zone for Technology and Innovation (HZQB-KCZYB-2020056), and Ganghong Young Scholar Development Fund (to Y.L.). Additional support was provided by the Hong Kong Branch of the CAS Center for Excellence in Animal Evolution and Genetics, Chinese University of Hong Kong (8601010)

More Information

Corresponding author: E-mail: leiyong@cuhk.edu.cn; shengu@cuhk.edu.hk
Received Date: 2022-12-30
Accepted Date: 2023-05-10

Published Online: 2023-05-10

Publish Date: 2023-05-18

Abstract

Abstract

Hereditary spastic paraplegia (HSP) is a group of genetic motor neuron diseases resulting from length-dependent axonal degeneration of the corticospinal upper motor neurons. Due to the advancement of next-generation sequencing, more than 70 novel HSP disease-causing genes have been identified in the past decade. Despite this, our understanding of HSP physiopathology and the development of efficient management and treatment strategies remain poor. One major challenge in studying HSP pathogenicity is selective neuronal vulnerability, characterized by the manifestation of clinical symptoms that are restricted to specific neuronal populations, despite the presence of germline disease-causing variants in every cell of the patient. Furthermore, disease genes may exhibit ubiquitous expression patterns and involve a myriad of different pathways to cause motor neuron degeneration. In the current review, we explore the correlation between transcriptomic data and clinical manifestations, as well as the importance of interspecies models by comparing tissue-specific transcriptomic profiles of humans and mice, expression patterns of different genes in the brain during development, and single-cell transcriptomic data from related tissues. Furthermore, we discuss the potential of emerging single-cell RNA sequencing technologies to resolve unanswered questions related to HSP pathogenicity.
- Hereditary spastic paraplegia,
- Motor neuron degeneration,
- Disease pathogenicity,
- Transcriptome analysis,
- Single-cell RNA sequencing

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