{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T16:16:56Z","timestamp":1775405816968,"version":"3.50.1"},"posted":{"date-parts":[[2023,3,20]]},"group-title":"Genomics","reference-count":76,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder caused by a CAG-polyglutamine repeat expansion. SCA7 patients display a striking loss of Purkinje cell (PC) neurons with disease progression; however, PCs are rare, making them difficult to characterize. We developed a PC nuclei enrichment protocol and applied it to single-nucleus RNA-seq of a SCA7 knock-in mouse model. Our results unify prior observations into a central mechanism of cell identity loss, impacting both glia and PCs, driving accumulation of inhibitory synapses and altered PC spiking. Zebrin-II subtype dysregulation is the predominant signal in PCs, leading to complete loss of zebrin-II striping at motor symptom onset in SCA7 mice. We show this zebrin-II subtype degradation is shared across Polyglutamine Ataxia mouse models and SCA7 patients. It has been speculated that PC subtype organization is critical for cerebellar function, and our results suggest that a breakdown of zebrin-II parasagittal striping is pathological.<\/jats:p>","DOI":"10.1101\/2023.03.19.533345","type":"posted-content","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T05:06:17Z","timestamp":1679288777000},"source":"Crossref","is-referenced-by-count":6,"title":["Purkinje-Enriched snRNA-seq in SCA7 Cerebellum Reveals Zebrin Identity Loss as a Central Feature of Polyglutamine Ataxias"],"prefix":"10.64898","author":[{"given":"Luke C.","family":"Bartelt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawel 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