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Single-cell profiling of long noncodingRNAsand their cell lineage commitment roles viaRNA-DNA-DNAtriplex formation in mammary epithelium

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机构: [1]State Key Laboratory of Genetic Resourcesand Evolution, Kunming Institute of Zoology,Chinese Academy of Sciences, Kunming,Yunnan, People’s Republic of China [2]Department of Urology, Shenzhen SecondPeople’s Hospital, The First Affiliated Hospitalof Shenzhen University, Shenzhen, People’sRepublic of China [3]International Cancer Center, ShenzhenUniversity School of Medicine, Shenzhen,People’s Republic of China [4]Yan’an Hospital Affiliated to KunmingMedical University, Kunming, Yunnan, People’sRepublic of China [5]Key Laboratory of Tumor ImmunologicalPrevention and Treatment of Yunnan Province [6]KIZ-CUHK Joint Laboratory of Bioresourcesand Molecular Research in Common Diseases,Kunming Institute of Zoology, ChineseAcademy of Sciences, Kunming, Yunnan,People’s Republic of China [7]Center for Excellence in Animal Evolution andGenetics, Chinese Academy of Sciences,Kunming, Yunnan, People’s Republic of China
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关键词: cell fate lncRNA mammary gland MaSCs scRNA-seq triplex structure

摘要:
Long noncoding RNAs (lncRNAs), which are crucial for organ development, exhibit cell-specific expression. Thus, transcriptomic analysis based on total tissue (bulk-seq) cannot accurately reflect the expression pattern of lncRNAs. Here, we used high-throughput single-cell RNA-seq data to investigate the role of lncRNAs using the hierarchical model of mammary epithelium. With our comprehensive annotation of the mammary epithelium, lncRNAs showed much greater cell-lineage specific expression than coding genes. The lineage-specific lncRNAs were functionally correlated with lineage commitment through the coding genes via thecis- andtrans-effects of lncRNAs. For the working mechanism, lncRNAs formed a triplex structure with the DNA helix to regulate downstream lineage-specific marker genes. We used lncRNA-Carmnas an example to validate the above findings.Carmn, which is specifically expressed in mammary gland stem cells (MaSCs) and basal cells, positively regulated the Wnt signaling ligandWnt10athrough formation of a lncRNA-DNA-DNA triplex, and thus controlled the stemness of MaSCs. Our study suggests that lncRNAs play essential roles in cell-lineage commitment and provides an approach to decipher lncRNA functions based on single-cell RNA-seq data.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 生物工程与应用微生物 2 区 细胞与组织工程 2 区 细胞生物学 2 区 血液学 2 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 生物工程与应用微生物 2 区 血液学 3 区 细胞与组织工程 3 区 细胞生物学 3 区 肿瘤学
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出版当年[2019]版:
Q1 CELL & TISSUE ENGINEERING Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 ONCOLOGY Q1 CELL BIOLOGY Q1 HEMATOLOGY
最新[2023]版:
Q1 HEMATOLOGY Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q2 CELL & TISSUE ENGINEERING Q2 CELL BIOLOGY Q2 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]State Key Laboratory of Genetic Resourcesand Evolution, Kunming Institute of Zoology,Chinese Academy of Sciences, Kunming,Yunnan, People’s Republic of China [2]Department of Urology, Shenzhen SecondPeople’s Hospital, The First Affiliated Hospitalof Shenzhen University, Shenzhen, People’sRepublic of China [3]International Cancer Center, ShenzhenUniversity School of Medicine, Shenzhen,People’s Republic of China
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通讯机构: [1]State Key Laboratory of Genetic Resourcesand Evolution, Kunming Institute of Zoology,Chinese Academy of Sciences, Kunming,Yunnan, People’s Republic of China [6]KIZ-CUHK Joint Laboratory of Bioresourcesand Molecular Research in Common Diseases,Kunming Institute of Zoology, ChineseAcademy of Sciences, Kunming, Yunnan,People’s Republic of China [7]Center for Excellence in Animal Evolution andGenetics, Chinese Academy of Sciences,Kunming, Yunnan, People’s Republic of China
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