Single-cell profiling of lncRNAs in human germ cells and molecular analysis reveals transcriptional regulation of LNC1845 on LHX8

SUMMARY 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. Here, we report the presence of many long non-coding RNAs (lncRNAs) which were specifically expressed in the germ cells during human gonadal development by single-cell profiling of the reported datasets, and the functional characterization of one divergent lncRNA, LNC1845 . 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, this study provides a comprehensive analysis of lncRNAs in developing germ cells and elucidates how a lncRNA function as a cis regulator during human germ cell development. GRAPHICAL ABSTRACT HIGHLIGHTS lncRNAs are expressed at significantly higher levels in both male and female germ cells than in somatic cells during human gonadal development. Divergent lncRNAs are enriched in the female meiotically and male mitotically arrested germ cells. LNC1845 regulates the transcriptional expression of LHX8 by modulating H3K4me3 and H3K27Ac levels.