{"title":"无活性-X 再激活过程中 X 缺失上调的特定系动态。","authors":"Hemant Chandru Naik, Deepshikha Chandel, Sudeshna Majumdar, Maniteja Arava, Runumi Baro, Harshavardhan Bv, Kishore Hari, Parichitran Ayyamperumal, Avinchal Manhas, Mohit Kumar Jolly, Srimonta Gayen","doi":"10.1016/j.stemcr.2024.10.001","DOIUrl":null,"url":null,"abstract":"<p><p>In mammals, X chromosome dosage is balanced between sexes through the silencing of one X chromosome in females. Recent single-cell RNA sequencing analysis demonstrated that the inactivation of the X chromosome is accompanied by the upregulation of the active X chromosome (Xa) during mouse embryogenesis. Here, we have investigated if the reactivation of inactive-X (Xi) leads to the loss of Xa upregulation in different cellular or developmental contexts. We find that while Xi reactivation and loss of Xa upregulation are tightly coupled in mouse embryonic epiblast and induced pluripotent stem cells, that is not the case in germ cells. Moreover, we demonstrate that partial reactivation of Xi in mouse extra-embryonic endoderm stem cells and human B cells does not result in the loss of Xa upregulation. Finally, we have established a mathematical model for the transcriptional coordination of two X chromosomes. Together, we conclude that the reactivation of Xi is not always synchronized with the loss of Xa upregulation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1564-1582"},"PeriodicalIF":5.9000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589478/pdf/","citationCount":"0","resultStr":"{\"title\":\"Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation.\",\"authors\":\"Hemant Chandru Naik, Deepshikha Chandel, Sudeshna Majumdar, Maniteja Arava, Runumi Baro, Harshavardhan Bv, Kishore Hari, Parichitran Ayyamperumal, Avinchal Manhas, Mohit Kumar Jolly, Srimonta Gayen\",\"doi\":\"10.1016/j.stemcr.2024.10.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In mammals, X chromosome dosage is balanced between sexes through the silencing of one X chromosome in females. Recent single-cell RNA sequencing analysis demonstrated that the inactivation of the X chromosome is accompanied by the upregulation of the active X chromosome (Xa) during mouse embryogenesis. Here, we have investigated if the reactivation of inactive-X (Xi) leads to the loss of Xa upregulation in different cellular or developmental contexts. We find that while Xi reactivation and loss of Xa upregulation are tightly coupled in mouse embryonic epiblast and induced pluripotent stem cells, that is not the case in germ cells. Moreover, we demonstrate that partial reactivation of Xi in mouse extra-embryonic endoderm stem cells and human B cells does not result in the loss of Xa upregulation. Finally, we have established a mathematical model for the transcriptional coordination of two X chromosomes. Together, we conclude that the reactivation of Xi is not always synchronized with the loss of Xa upregulation.</p>\",\"PeriodicalId\":21885,\"journal\":{\"name\":\"Stem Cell Reports\",\"volume\":\" \",\"pages\":\"1564-1582\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-11-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589478/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stem Cell Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stemcr.2024.10.001\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stemcr.2024.10.001","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/31 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0
摘要
在哺乳动物中,X 染色体的剂量通过雌性的一条 X 染色体沉默而在两性之间实现平衡。最近的单细胞 RNA 测序分析表明,在小鼠胚胎发育过程中,X 染色体的失活伴随着活性 X 染色体(Xa)的上调。在此,我们研究了非活性-X(Xi)的再激活是否会导致 Xa 在不同细胞或发育环境中失去上调。我们发现,在小鼠胚胎上胚层和诱导多能干细胞中,Xi 的再激活和 Xa 上调的丧失是紧密联系在一起的,但在生殖细胞中却不是这样。此外,我们还证明,在小鼠胚外内胚层干细胞和人类 B 细胞中,Xi 的部分再激活不会导致 Xa 上调的丧失。最后,我们建立了两个 X 染色体转录协调的数学模型。综上所述,我们得出结论:Xi 的重新激活并不总是与 Xa 上调的丧失同步进行。
Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation.
In mammals, X chromosome dosage is balanced between sexes through the silencing of one X chromosome in females. Recent single-cell RNA sequencing analysis demonstrated that the inactivation of the X chromosome is accompanied by the upregulation of the active X chromosome (Xa) during mouse embryogenesis. Here, we have investigated if the reactivation of inactive-X (Xi) leads to the loss of Xa upregulation in different cellular or developmental contexts. We find that while Xi reactivation and loss of Xa upregulation are tightly coupled in mouse embryonic epiblast and induced pluripotent stem cells, that is not the case in germ cells. Moreover, we demonstrate that partial reactivation of Xi in mouse extra-embryonic endoderm stem cells and human B cells does not result in the loss of Xa upregulation. Finally, we have established a mathematical model for the transcriptional coordination of two X chromosomes. Together, we conclude that the reactivation of Xi is not always synchronized with the loss of Xa upregulation.
期刊介绍:
Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.