ArticleCommunications biology2024
Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 2 citations in OpenAlex.
- Advancements in differentiation of induced pluripotent stem cells into specialized neuronal subtypes.Neural regeneration research · 2026Article
- Wild-type C9orf72 drives proteasomal dysfunction and mutant aggregates via a Stat1-Isg15 axis in Huntington's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Translational Relevance of SCA1 Models for the Development of Therapies for Spinocerebellar Ataxia Type 1.Biomedicines · 2025Review
- Roots of Progress: Uncovering Cerebellar Ataxias Using iPSC Models.Biomedicines · 2025Review
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Authors and funding
12 authors at 5 institutions in 1 country.
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Abstract
Better understanding of the earliest molecular pathologies of all neurodegenerative diseases is expected to improve human therapeutics. We investigated the earliest molecular pathology of spinocerebellar ataxia type 1 (SCA1), a rare familial neurodegenerative disease that primarily induces death and dysfunction of cerebellum Purkinje cells. Extensive prior studies have identified involvement of transcription or RNA-splicing factors in the molecular pathology of SCA1. However, the regulatory network of SCA1 pathology, especially central regulators of the earliest developmental stages and inflammatory events, remains incompletely understood. Here, we elucidated the earliest developmental pathology of SCA1 using originally developed dynamic molecular network analyses of sequentially acquired RNA-seq data during differentiation of SCA1 patient-derived induced pluripotent stem cells (iPSCs) to Purkinje cells. Dynamic molecular network analysis implicated histone genes and cytokine-relevant immune response genes at the earliest stages of development, and revealed relevance of ISG15 to the following degradation and accumulation of mutant ataxin-1 in Purkinje cells of SCA1 model mice and human patients.
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