{"doi":"10.7554/elife.101918","title":"Identification and characterization of early human photoreceptor states and cell-state-specific retinoblastoma-related features","abstract":"Human cone photoreceptors differ from rods and serve as the retinoblastoma cell-of-origin, yet the developmental basis for their distinct behaviors is poorly understood. Here, we used deep full-length single-cell RNA-sequencing (scRNA-seq) to distinguish post-mitotic cone and rod developmental states and identify cone-specific features related to retinoblastomagenesis. The analyses revealed nascent, immediately post-mitotic cone and rod precursors characterized by higher THRB or NRL regulon activities, immature and maturing cone and rod precursors with concurrent cone- and rod-related gene and regulon expression, and distinct early and late cone and rod maturation states distinguished by maturation-associated declines in RAX regulon activity. Cell-state-specific gene expression features inferred from full-length scRNA-seq were consistent with past 3' scRNA-seq analyses. Beyond the cell state characterizations, full-length scRNA-seq revealed that both L/M cone and rod precursors co-expressed NRL and THRB RNAs yet differentially expressed functionally antagonistic NRL isoforms and prematurely terminated THRB transcripts. Moreover, early L/M cone precursors sequentially expressed several lncRNAs along with MYCN , which composed the seventh most L/M-cone-specific regulon, and SYK , which was implicated in the cone precursors’ proliferative response to RB1 loss. These findings reveal previously unresolved photoreceptor precursor states and suggest a role for early cone-precursor-intrinsic SYK expression in retinoblastoma initiation.","journal":"eLife","year":2024,"id":492463,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9185,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE207802"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":383467,"name":"Kevin Stachelek","orcid":"0000-0003-2085-695X","position":1,"is_corresponding":false},{"id":422143,"name":"Linda Cambier","orcid":"0000-0001-9482-1413","position":2,"is_corresponding":false},{"id":418040,"name":"Sunhye Lee","orcid":"0000-0002-4825-745X","position":3,"is_corresponding":false},{"id":1138744,"name":"Jinlun Bai","orcid":null,"position":4,"is_corresponding":false},{"id":1339173,"name":"B. K. Bhat","orcid":null,"position":5,"is_corresponding":false},{"id":317490,"name":"Mark W. Reid","orcid":"0000-0002-1942-225X","position":6,"is_corresponding":false},{"id":1834,"name":"Daniel J. Weisenberger","orcid":"0000-0001-8303-2603","position":7,"is_corresponding":false},{"id":730171,"name":"Jennifer G. Aparicio","orcid":"0000-0002-6442-3032","position":8,"is_corresponding":false},{"id":1174500,"name":"Yeha Kim","orcid":null,"position":9,"is_corresponding":false},{"id":1174501,"name":"Mitali Singh","orcid":null,"position":10,"is_corresponding":false},{"id":629583,"name":"Maxwell Bay","orcid":null,"position":11,"is_corresponding":false},{"id":298156,"name":"Matthew E. Thornton","orcid":"0000-0002-1083-2703","position":12,"is_corresponding":false},{"id":1174502,"name":"Eamon K Doyle","orcid":null,"position":13,"is_corresponding":false},{"id":473401,"name":"Zachary Fouladian","orcid":"0000-0003-1447-8884","position":14,"is_corresponding":false},{"id":1174503,"name":"Stephan G Erberich","orcid":null,"position":15,"is_corresponding":false},{"id":298158,"name":"Brendan H. Grubbs","orcid":"0000-0002-1963-4922","position":16,"is_corresponding":false},{"id":559565,"name":"Michael A. Bonaguidi","orcid":"0000-0002-9295-4762","position":17,"is_corresponding":false},{"id":729679,"name":"Cheryl M. 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