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深圳市第二人民医院深圳市康宁医院深圳医学信息中心[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
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.
基金:
National Key Research and Development Program of China [2016YFA0100900]; National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31970612, U1802285]; Yunnan Applied Basic Research Key Projects [2015HA026, 2018FA002, 2019FB047]
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
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Xu Haibo,Yang Xing,Huang Weiren,et al.Single-cell profiling of long noncodingRNAsand their cell lineage commitment roles viaRNA-DNA-DNAtriplex formation in mammary epithelium[J].STEM CELLS.2020,38(12):1594-1611.doi:10.1002/stem.3274.
APA:
Xu, Haibo,Yang, Xing,Huang, Weiren,Ma, Yujie,Ke, Hao...&Jiao, Baowei.(2020).Single-cell profiling of long noncodingRNAsand their cell lineage commitment roles viaRNA-DNA-DNAtriplex formation in mammary epithelium.STEM CELLS,38,(12)
MLA:
Xu, Haibo,et al."Single-cell profiling of long noncodingRNAsand their cell lineage commitment roles viaRNA-DNA-DNAtriplex formation in mammary epithelium".STEM CELLS 38..12(2020):1594-1611