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 sequ...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.展开更多
基金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)+4 种基金National Natural Science Foundation of China(32170583,82202045)Hong Kong RGCCRF Equipment Fund C5033-19EShenzhen-Hong Kong Cooperation Zone for Technology and Innovation(HZQB-KCZYB-2020056)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)。
文摘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.
