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The aim of this study was to systematically map the transcriptional changes that occur in the degenerating mouse retina at the single cell level. To this end, we employed single-cell RNA-sequencing (scRNA-seq) and retinal degeneration-1 (rd1) mice to profile the impact of the disease mutation on the diverse retinal cell types during early post-natal development. The transcriptome data allowed to annotate 43,979 individual cells grouped into 20 distinct clusters. We further characterized cluster-specific metabolic and biological changes in individual cell types. Our results highlight Ca2+-signaling as relevant to hereditary photoreceptor degeneration. Although metabolic reprogramming in retina, known as the \u2018Warburg effect\u2019, has been documented, further metabolic changes were noticed in rd1 mice. Such metabolic changes in rd1 mutation was likely regulated through mitogen-activated protein kinase (MAPK) pathway. By combining single-cell transcriptomes and immunofluorescence staining, our study revealed cell type-specific changes in gene expression, as well as interplay between Ca2+-induced cell death and metabolic pathways.<\/jats:p>","DOI":"10.3390\/ijms232012170","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T20:53:29Z","timestamp":1665608009000},"page":"12170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Single-Cell Transcriptomic Profiling in Inherited Retinal Degeneration Reveals Distinct Metabolic Pathways in Rod and Cone Photoreceptors"],"prefix":"10.3390","volume":"23","author":[{"given":"Yiyi","family":"Chen","sequence":"first","affiliation":[{"name":"Institute for Ophthalmic Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Graduate Training Centre of Neuroscience, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3246-5913","authenticated-orcid":false,"given":"Yujie","family":"Dong","sequence":"additional","affiliation":[{"name":"Yunnan Eye Institute & Key Laboratory of Yunnan Province, 650021 Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7776-7838","authenticated-orcid":false,"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Graduate Training Centre of Neuroscience, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Graduate Training Centre of Neuroscience, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Yu","sequence":"additional","affiliation":[{"name":"Graduate Training Centre of Neuroscience, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-5993","authenticated-orcid":false,"given":"Kangwei","family":"Jiao","sequence":"additional","affiliation":[{"name":"Yunnan Eye Institute & Key Laboratory of Yunnan Province, 650021 Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-5742","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Paquet-Durand","sequence":"additional","affiliation":[{"name":"Institute for Ophthalmic Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0039-6257(88)90085-9","article-title":"Retinitis pigmentosa","volume":"33","author":"Pagon","year":"1988","journal-title":"Surv. 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