{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T01:57:05Z","timestamp":1783475825770,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Inner Mongolia Scientific and Technological Achievement Transformation","award":["2020CG0078"],"award-info":[{"award-number":["2020CG0078"]}]},{"name":"Inner Mongolia Scientific and Technological Achievement Transformation","award":["219GG348"],"award-info":[{"award-number":["219GG348"]}]},{"name":"Inner Mongolia Scientific and Technological Achievement Transformation","award":["2020ZD0007"],"award-info":[{"award-number":["2020ZD0007"]}]},{"name":"Inner Mongolia Scientific and Technological Achievement Transformation","award":["2020GG0055"],"award-info":[{"award-number":["2020GG0055"]}]},{"name":"Inner Mongolia Scientific and Technological Achievement Transformation","award":["2021GG0062"],"award-info":[{"award-number":["2021GG0062"]}]},{"name":"Inner Mongolia Scientific and Technological Achievement Transformation","award":["31860689"],"award-info":[{"award-number":["31860689"]}]},{"name":"Science and Technology Planning Project of Inner Mongolia","award":["2020CG0078"],"award-info":[{"award-number":["2020CG0078"]}]},{"name":"Science and Technology Planning Project of Inner Mongolia","award":["219GG348"],"award-info":[{"award-number":["219GG348"]}]},{"name":"Science and Technology Planning Project of Inner Mongolia","award":["2020ZD0007"],"award-info":[{"award-number":["2020ZD0007"]}]},{"name":"Science and Technology Planning Project of Inner Mongolia","award":["2020GG0055"],"award-info":[{"award-number":["2020GG0055"]}]},{"name":"Science and Technology Planning Project of Inner Mongolia","award":["2021GG0062"],"award-info":[{"award-number":["2021GG0062"]}]},{"name":"Science and Technology Planning Project of Inner Mongolia","award":["31860689"],"award-info":[{"award-number":["31860689"]}]},{"name":"National Natural Science Foundation of China","award":["2020CG0078"],"award-info":[{"award-number":["2020CG0078"]}]},{"name":"National Natural Science Foundation of China","award":["219GG348"],"award-info":[{"award-number":["219GG348"]}]},{"name":"National Natural Science Foundation of China","award":["2020ZD0007"],"award-info":[{"award-number":["2020ZD0007"]}]},{"name":"National Natural Science Foundation of China","award":["2020GG0055"],"award-info":[{"award-number":["2020GG0055"]}]},{"name":"National Natural Science Foundation of China","award":["2021GG0062"],"award-info":[{"award-number":["2021GG0062"]}]},{"name":"National Natural Science Foundation of China","award":["31860689"],"award-info":[{"award-number":["31860689"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Dosage compensation is a mechanism first proposed by Susumu Ohno, whereby X inactivation balances X gene output between males (XY) and females (XX), while X upregulation balances X genes with autosomal gene output. These mechanisms have been actively studied in Drosophila and mice, but research regarding them lags behind in domestic species. It is unclear how the X chromosome is regulated in the sheep male germline. To address this, using single-cell RNA sequencing, we analyzed testes in three important developmental stages of sheep. We observed that the total RNA per cell from X and autosomes peaked in SSCs and spermatogonia and was then reduced in early spermatocytes. Furthermore, we counted the detected reads per gene in each cell type for X and autosomes. In cells experiencing dose compensation, close proximity to MSL (male-specific lethal), which is regulated the active X chromosome and was observed. Our results suggest that there is no dose compensation in the pre-meiotic germ cells of sheep testes and, in addition, MSL1 and MSL2 are expressed in early germ cells and involved in regulating mammalian X-chromosome inactivation and activation.<\/jats:p>","DOI":"10.3390\/ani12172169","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T21:03:51Z","timestamp":1661375031000},"page":"2169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dosage Compensation of the X Chromosome during Sheep Testis Development Revealed by Single-Cell RNA Sequencing"],"prefix":"10.3390","volume":"12","author":[{"given":"Jie","family":"Su","sequence":"first","affiliation":[{"name":"Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agriculture University, Hohhot 010018, China"},{"name":"Department of Psychosomatic Medicine, Inner Mongolia Medical University, Hohhot 010030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agriculture University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Su","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agriculture University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agriculture University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agriculture University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Academy of Agriculture & Animal Husbandry Sciences, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiunan","family":"Li","sequence":"additional","affiliation":[{"name":"Inner Mongolia Academy of Agriculture & Animal Husbandry Sciences, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangmei","family":"Qi","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agriculture University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijun","family":"Li","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agriculture University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xihe","family":"Li","sequence":"additional","affiliation":[{"name":"Inner Mongolia Saikexing Institutes of Breeding and Reproductive Biotechnologies in Domestic Animal, Hohhot 011517, China"},{"name":"Research Center for Animal Genetic Resources of Mongolia Plateau, College of Life Science, Inner Mongolia University, Hohhot 010021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9184-7853","authenticated-orcid":false,"given":"Yongli","family":"Song","sequence":"additional","affiliation":[{"name":"Research Center for Animal Genetic Resources of Mongolia Plateau, College of Life Science, Inner Mongolia University, Hohhot 010021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifang","family":"Cao","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Basic Veterinary Science, Inner Mongolia Agriculture University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Huang, K., Zeng, Q., Feng, Y., Hu, Y., An, Q., Li, T., Qin, L.J., Liu, J.Y., Xue, Z., and Fan, G. (2020). X-chromosome dosage compensation dynamics in human early embryos. bioRxiv.","DOI":"10.1101\/2020.03.08.982694"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ohno, S. (1966). Sex Chromosomes and Sex-Linked Genes, Springer.","DOI":"10.1007\/978-3-662-35113-0"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Julien, P., Brawand, D., Soumillon, M., Necsulea, A., Liechti, A., Sch\u00fctz, F., Daish, T., Gr\u00fctzner, F., Kaessmann, H., and Barton, N.H. (2012). Mechanisms and Evolutionary Patterns of Mammalian and Avian Dosage Compensation. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001328"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1534\/g3.118.200815","article-title":"Dosage Compensation and Gene Expression of the X Chromosome in Sheep","volume":"9","author":"Duan","year":"2018","journal-title":"G3 Genesgenetics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng1705","article-title":"Dosage compensation of the active X chromosome in mammals","volume":"38","author":"Di","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1071\/RDv28n2Ab144","article-title":"144 Dosage Compensation and X-Linked Gene Expression in Bovine In Vivo and In Vitro Embryos","volume":"28","author":"Duan","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/jbiol30","article-title":"Global analysis of X-chromosome dosage compensation","volume":"5","author":"Gupta","year":"2006","journal-title":"J. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/ng.948","article-title":"Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster","volume":"43","author":"Deng","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/ng.991","article-title":"Evidence for dosage compensation between the X chromosome and autosomes in mammals","volume":"43","author":"Kharchenko","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1128\/MMBR.62.2.362-378.1998","article-title":"Regulation of X-Chromosome Inactivation in Development in Mice and Humans","volume":"62","author":"Goto","year":"1998","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"dev.184259","DOI":"10.1242\/dev.184259","article-title":"Single-cyst transcriptome analysis of Drosophila male germline stem cell lineage","volume":"147","author":"Shi","year":"2020","journal-title":"Development"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Witt, E., Shao, Z., Hu, C., Krause, H.M., and Zhao, L. (2021). Single-cell RNA-sequencing reveals pre-meiotic X-chromosome dosage compensation in Drosophila testis. PLoS Genet., 17.","DOI":"10.1101\/2021.02.05.429952"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Argyridou, E., and Parsch, J. (2018). Regulation of the X Chromosome in the Germline and Soma of Drosophila melanogaster Males. Genes, 9.","DOI":"10.3390\/genes9050242"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Meiklejohn, C.D., Landeen, E.L., Cook, J.M., Kingan, S.B., and Presgraves, D.C. (2011). Sex Chromosome-Specific Regulation in the Drosophila Male Germline But Little Evidence for Chromosomal Dosage Compensation or Meiotic Inactivation. PLoS Biol., 9.","DOI":"10.1371\/journal.pbio.1001126"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ceb.2009.04.012","article-title":"X inactivation and the complexities of silencing a sex chromosome","volume":"21","author":"Chow","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s11171-005-0045-1","article-title":"Tissue Specificity of Alternative Splicing of Transcripts Encoding Hampin, a New Mouse Protein Homologous to the Drosophila MSL-1 Protein","volume":"31","author":"Dmitriev","year":"2005","journal-title":"Russ. J. Bioorganic Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6798","DOI":"10.1128\/MCB.25.15.6798-6810.2005","article-title":"hMOF Histone Acetyltransferase Is Required for Histone H4 Lysine 16 Acetylation in Mammalian Cells","volume":"25","author":"Taipale","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6621","DOI":"10.1093\/nar\/gkl989","article-title":"Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3","volume":"34","author":"Peng","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1128\/MCB.25.8.2924-2937.2005","article-title":"MRG15 Regulates Embryonic Development and Cell Proliferation","volume":"25","author":"Tominaga","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.bbrc.2007.02.073","article-title":"Characterization of hampin\/MSL1 as a node in the nuclear interactome","volume":"355","author":"Dmitriev","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.molcel.2011.05.015","article-title":"The RING Finger Protein MSL2 in the MOF Complex Is an E3Ubiquitin Ligase for H2B K34 and Is Involved in Crosstalk with H3 K4 and K79 Methylation","volume":"43","author":"Wu","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.devcel.2013.01.028","article-title":"Mammalian X upregulation is associated with enhanced transcription initiation, RNA half-life, and MOF-mediated H4K16 acetylation","volume":"25","author":"Deng","year":"2013","journal-title":"Dev. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.devcel.2016.12.023","article-title":"Non-Canonical and Sexually Dimorphic X Dosage Compensation States in the Mouse and Human Germline","volume":"40","author":"Sangrithi","year":"2017","journal-title":"Dev. Cell"},{"key":"ref_24","first-page":"e21187","article-title":"Characterization of sheep spermatogenesis through single cell RNA sequencing","volume":"35","author":"Yang","year":"2020","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.stem.2020.12.004","article-title":"Single-cell analysis of the developing human testis reveals somatic niche cell specification and fetal germline stem cell establishment","volume":"28","author":"Guo","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"(2018). The adult human testis transcriptional cell atlas. Cell Res., 28, 1141\u20131157.","DOI":"10.1038\/s41422-018-0099-2"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.devcel.2018.07.025","article-title":"A Comprehensive Roadmap of Murine Spermatogenesis Defined by Single-Cell RNA-Seq","volume":"46","author":"Daniel","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.1038\/s41598-018-24725-0","article-title":"Characterization of germ cell differentiation in the male mouse through single-cell RNA sequencing","volume":"8","author":"Lukassen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev-genet-112414-055145","article-title":"Meiotic Silencing in Mammals","volume":"49","author":"Turner","year":"2015","journal-title":"Annu. Rev. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1530\/rep.0.1250769","article-title":"Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood","volume":"125","author":"Sharpe","year":"2003","journal-title":"Reproduction"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Meyts, E.R.D., Almstrup, K., Nielsen, J.E., and Skakkeb\u00e6k, N.E. (2013). The Testis in Childhood Between Birth and Puberty, Springer.","DOI":"10.1007\/978-1-4471-2763-5_6"},{"key":"ref_32","first-page":"395","article-title":"Testis and epididymis","volume":"58","author":"Skandalakis","year":"1983","journal-title":"J. Reprod. Fertil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1093\/gbe\/evx154","article-title":"Evolution of Sex Chromosome Dosage Compensation in Animals: A Beautiful Theory, Undermined by Facts and Bedeviled by Details","volume":"9","author":"Gu","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0925-4773(98)00009-4","article-title":"An analysis of maleless and histone H4 acetylation in Drosophila melanogaster spermatogenesis","volume":"71","author":"Rastelli","year":"1998","journal-title":"Mech. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1101\/gad.8.1.96","article-title":"Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila","volume":"8","author":"Bone","year":"1994","journal-title":"Genes Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1101\/gad.1343705","article-title":"Global regulation of X chromosomal genes by the MSL complex in Drosophila melanogaster","volume":"19","author":"Hamada","year":"2005","journal-title":"Genes Dev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gde.2015.03.007","article-title":"The MSL complex: Juggling RNA-protein interactions for dosage compensation and beyond","volume":"31","author":"Keller","year":"2015","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.molcel.2010.05.021","article-title":"The nonspecific lethal complex is a transcriptional regulator in Drosophila","volume":"38","author":"Raja","year":"2010","journal-title":"Mol. Cell"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/17\/2169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:14:37Z","timestamp":1760141677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/12\/17\/2169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ani12172169"],"URL":"https:\/\/doi.org\/10.3390\/ani12172169","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,24]]}}}