論文 - 詳細
| RRC ID | 78800 |
|---|---|
| 著者 | Homma H, Yoshioka Y, Fujita K, Shirai S, Hama Y, Komano H, Saito Y, Yabe I, Okano H, Sasaki H, Tanaka H, Okazawa H. |
| タイトル | Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage. |
| ジャーナル | Commun Biol |
| 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. |
| 巻・号 | 7(1) |
| ページ | 413 |
| 公開日 | 2024-4-9 |
| DOI | 10.1038/s42003-024-06066-z |
| PII | 10.1038/s42003-024-06066-z |
| PMID | 38594382 |
| PMC | PMC11003991 |
| MeSH | Animals Cytokines Humans Induced Pluripotent Stem Cells* / pathology Mice Mice, Transgenic Purkinje Cells / physiology Spinocerebellar Ataxias* / genetics Spinocerebellar Ataxias* / pathology Ubiquitins |
| IF | 4.165 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 201B7(HPS0063) |