Single-cell profiling of lncRNAs in human germ cells and molecular analysis reveals transcriptional regulation of LNC1845 on LHX8
Nan Wang,
Jing He,
Xiaoyu Feng,
Shengyou Liao,
Yi Zhao,
Fuchou Tang,
Kehkooi Kee
Affiliations
Nan Wang
Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
Jing He
Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
Xiaoyu Feng
Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
Shengyou Liao
Key Laboratory of Intelligent Information Processing, Advanced Computer Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China
Yi Zhao
Key Laboratory of Intelligent Information Processing, Advanced Computer Research Center, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, China
Fuchou Tang
Biodynamic Optical Imaging Center & Department of Obstetrics and Gynecology, College of Life Sciences, Third Hospital, Peking University, Beijing, China
Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
Non-coding RNAs exert diverse functions in many cell types. In addition to transcription factors from coding genes, non-coding RNAs may also play essential roles in shaping and directing the fate of germ cells. The presence of many long non-coding RNAs (lncRNAs) which are specifically expressed in the germ cells during human gonadal development were reported and one divergent lncRNA, LNC1845, was functionally characterized. Comprehensive bioinformatic analysis of these lncRNAs indicates that divergent lncRNAs occupied the majority of female and male germ cells. Integrating lncRNA expression into the bioinformatic analysis also enhances the cell-type classification of female germ cells. Functional dissection using in vitro differentiation of human pluripotent stem cells to germ cells revealed the regulatory role of LNC1845 on a transcription factor essential for ovarian follicle development, LHX8, by modulating the levels of histone modifications, H3K4me3 and H3K27Ac. Hence, bioinformatical analysis and experimental verification provide a comprehensive analysis of lncRNAs in developing germ cells and elucidate how an lncRNA function as a cis regulator during human germ cell development.
