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

Decoding hereditary spastic paraplegia pathogenicity through transcriptomic profiling

doi: 10.24272/j.issn.2095-8137.2022.281
The HSP genes used in this study are available via the OMIM PS303350 phenotypic series (https://omim.org/phenotypicSeries/PS303350) (last accessed on 14 September 2021). The tissue-specific transcriptomic datasets analyzed in this study are available via the v20 Human Protein Atlas portal (https://v20.proteinatlas.org/) (last accessed on 14 November 2021). The expression data with developmental time are accessible via the EMBL-EBI Expression Atlas portal (https://www.ebi.ac.uk/gxa/home) (last accessed on 11 December 2021). The scRNA-seq datasets are available from the Allen Institute cell-type database (RNA-Seq Data) (https://portal.brain-map.org/atlases-and-data/rnaseq) (last accessed on 28 December 2021). The mouse motor cortical Patch-seq dataset is available at GitHub (https://github.com/berenslab/mini-atlas) (last accessed on 9 June 2022). The cross-species snRNA-seq dataset is available via Cytosplore Viewer (https://viewer.cytosplore.org/) (last accessed on 10 June 2022). The pLI scores are available from the gnomAD browser (https://gnomad.broadinstitute.org/) (last accessed on 20 May 2022). The CFG scores of HSP genes are available from the AlzData database (http://alzdata.org/) (last accessed on 24 November 2022).
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
  • 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.
  • The HSP genes used in this study are available via the OMIM PS303350 phenotypic series (https://omim.org/phenotypicSeries/PS303350) (last accessed on 14 September 2021). The tissue-specific transcriptomic datasets analyzed in this study are available via the v20 Human Protein Atlas portal (https://v20.proteinatlas.org/) (last accessed on 14 November 2021). The expression data with developmental time are accessible via the EMBL-EBI Expression Atlas portal (https://www.ebi.ac.uk/gxa/home) (last accessed on 11 December 2021). The scRNA-seq datasets are available from the Allen Institute cell-type database (RNA-Seq Data) (https://portal.brain-map.org/atlases-and-data/rnaseq) (last accessed on 28 December 2021). The mouse motor cortical Patch-seq dataset is available at GitHub (https://github.com/berenslab/mini-atlas) (last accessed on 9 June 2022). The cross-species snRNA-seq dataset is available via Cytosplore Viewer (https://viewer.cytosplore.org/) (last accessed on 10 June 2022). The pLI scores are available from the gnomAD browser (https://gnomad.broadinstitute.org/) (last accessed on 20 May 2022). The CFG scores of HSP genes are available from the AlzData database (http://alzdata.org/) (last accessed on 24 November 2022).
    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.
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