{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:20:24Z","timestamp":1788394824691,"version":"build-2803163510"},"reference-count":107,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA HD000139"],"award-info":[{"award-number":["ZIA HD000139"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001790","name":"Ara Parseghian Medical Research Foundation","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100001790","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann\u2013Pick disease, type C1 (NPC1) is a lysosomal disease characterized by endolysosomal storage of unesterified cholesterol and decreased cellular cholesterol bioavailability. A cardinal symptom of NPC1 is cerebellar ataxia due to Purkinje neuron loss. To gain an understanding of the cerebellar neuropathology we obtained single cell transcriptome data from control (Npc1+\/+) and both three-week-old presymptomatic and seven-week-old symptomatic mutant (Npc1\u2212\/\u2212) mice. In seven-week-old Npc1\u2212\/\u2212 mice, differential expression data was obtained for neuronal, glial, vascular, and myeloid cells. As anticipated, we observed microglial activation and increased expression of innate immunity genes. We also observed increased expression of innate immunity genes by other cerebellar cell types, including Purkinje neurons. Whereas neuroinflammation mediated by microglia may have both neuroprotective and neurotoxic components, the contribution of increased expression of these genes by non-immune cells to NPC1 pathology is not known. It is possible that dysregulated expression of innate immunity genes by non-immune cells is neurotoxic. We did not anticipate a general lack of transcriptomic changes in cells other than microglia from presymptomatic three-week-old Npc1\u2212\/\u2212 mice. This observation suggests that microglia activation precedes neuronal dysfunction. The data presented in this paper will be useful for generating testable hypotheses related to disease progression and Purkinje neurons loss as well as providing insight into potential novel therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms21155368","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T07:31:45Z","timestamp":1596007905000},"page":"5368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Single Cell Transcriptome Analysis of Niemann\u2013Pick Disease, Type C1 Cerebella"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-7540","authenticated-orcid":false,"given":"Antony","family":"Cougnoux","sequence":"first","affiliation":[{"name":"Division of Translational Medicine, <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia C.","family":"Yerger","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason","family":"Fellmeth","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Serra-Vinardell","sequence":"additional","affiliation":[{"name":"Human Biochemical Genetics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Navid","sequence":"additional","affiliation":[{"name":"Pediatric Translational Research Branch, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Iben","sequence":"additional","affiliation":[{"name":"Molecular Genomic Core, <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Wassif","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2785-5941","authenticated-orcid":false,"given":"Niamh X.","family":"Cawley","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-0046","authenticated-orcid":false,"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"10CRC, Rm. 5-2571, 10 Center Dr., Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.277.5323.228","article-title":"Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis","volume":"277","author":"Carstea","year":"1997","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9290","DOI":"10.1074\/jbc.M111.326405","article-title":"Normalization of cholesterol homeostasis by 2-hydroxypropyl-beta-cyclodextrin in neurons and glia from Niemann-Pick C1 (NPC1)-deficient mice","volume":"287","author":"Peake","year":"2012","journal-title":"J. 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