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Here, we employed single-cell transcriptomics to identify genes involved in reproductive development in the trematode model Schistosoma mansoni. This parasite causes schistosomiasis, a major neglected infectious disease affecting &amp;gt;240 million people worldwide. The pathology of schistosomiasis is closely associated with schistosome eggs deposited in host organs including the liver. Unlike other trematodes, schistosomes exhibit distinct sexes, with egg production reliant on the pairing-dependent maturation of female reproductive organs. Despite this significance, the molecular mechanisms underlying ovary development and oocyte differentiation remain largely unexplored. Utilizing an organ isolation approach for S. mansoni, we extracted ovaries of paired females followed by single-cell RNA sequencing (RNA-seq) with disassociated oocytes. A total of 1967 oocytes expressing 7872 genes passed quality control (QC) filtering. Unsupervised clustering revealed four distinct cell clusters: somatic, germ cells and progeny, intermediate and late germ cells. Among distinct marker genes for each cluster, we identified a hitherto uncharacterized transcription factor of the retinoic acid receptor family, SmRAR. Functional analyses of SmRAR and associated genes like Smmeiob (meiosis-specific, oligonucleotide\/oligosaccharide binding motif (OB) domain-containing) demonstrated their pairing-dependent and ovary-preferential expression and their decisive roles in oocyte differentiation of S. mansoni.<\/jats:p>","DOI":"10.1093\/nar\/gkae1228","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T10:09:30Z","timestamp":1734343770000},"source":"Crossref","is-referenced-by-count":20,"title":["The retinoic acid family-like nuclear receptor SmRAR identified by single-cell transcriptomics of ovarian cells controls oocyte differentiation in <i>Schistosoma mansoni<\/i>"],"prefix":"10.1093","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5007-3687","authenticated-orcid":false,"given":"Max F","family":"Moescheid","sequence":"first","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University , Schubertstrasse 81, 35392 Giessen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University , Schubertstrasse 81, 35392 Giessen ,","place":["Germany"]},{"name":"Wellcome Sanger Institute , Wellcome Genome Campus, Hinxton CB10, 1SA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Diaz","family":"Soria","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute , Wellcome Genome Campus, Hinxton CB10, 1SA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Quack","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University , Schubertstrasse 81, 35392 Giessen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Puckelwaldt","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University , Schubertstrasse 81, 35392 Giessen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Holroyd","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute , Wellcome Genome Campus, Hinxton CB10, 1SA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Holzaepfel","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University , Schubertstrasse 81, 35392 Giessen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1932-9696","authenticated-orcid":false,"given":"Simone","family":"Haeberlein","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University , Schubertstrasse 81, 35392 Giessen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute , Wellcome Genome Campus, Hinxton CB10, 1SA ,","place":["UK"]},{"name":"Department of Life Sciences, Aberystwyth University , Penglais, Aberystwyth , Ceredigion, SY23 3DA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Berriman","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute , Wellcome Genome Campus, Hinxton CB10, 1SA ,","place":["UK"]},{"name":"School of Infection and Immunity, College of Medicine, Veterinary and Life Sciences, University of Glasgow , 120 University Place, Glasgow G12 8TA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph G","family":"Grevelding","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University , Schubertstrasse 81, 35392 Giessen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"2025030421245785100_B1","doi-asserted-by":"crossref","first-page":"a016709","DOI":"10.1101\/cshperspect.a016709","article-title":"Signaling by nuclear receptors","volume":"5","author":"Sever","year":"2013","journal-title":"Cold Spring Harb. 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