Divergent long noncoding RNAs (lncRNAs) represent a major lncRNA biotype in mouse and human genomes. The biological and molecular functions of the divergent lncRNAs remain largely unknown. Here, we show that , a divergent lncRNA for gene, is conserved among five mammalian species and highly expressed in embryonic stem cells (ESCs) and early embryos. knockout impairs ESC self-renewal and causes early embryonic lethality. can activate Zbtb3 by promoting the assembly and ATPase activity of Snf2-related CREBBP activator protein (SRCAP) complex in Zbtb3 potentiates the ESC self-renewal in a Nanog-dependent manner. Finally, deficiency impairs the ESC self-renewal and early embryonic development. Therefore, our findings reveal that lncRNAs may represent an additional layer of the regulation of ESC self-renewal and early embryogenesis.

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Purpose Ovarian aging is closely tied to the decline in ovarian follicular reserve and oocyte quality. During the prolonged reproductive lifespan of the female, granulosa cells connected with oocytes play critical roles in maintaining follicle reservoir, oocyte growth and follicular development. We tested whether double-strand breaks (DSBs) and repair in granulosa cells within the follicular reservoir are associated with ovarian aging. Methods Ovaries were sectioned and processed for epifluorescence microscopy, confocal microscopy, and immunohistochemistry. DNA damage was revealed by immunstaining of γH2AX foci and telomere damage by γH2AX foci colocalized with telomere associated protein TRF2. DNA repair was indicated by BRCA1 immunofluorescence.Results DSBs in granulosa cells increase and DSB repair ability, characterized by BRCA1 foci, decreases with advancing age. γH2AX foci increase in primordial, primary and secondary follicles with advancing age. Likewise, telomere damage increases with advancing age. In contrast, BRCA1 foci in granulosa cells of primordial, primary and secondary follicles decrease with monkey age. BRCA1 positive foci in the oocyte nuclei also decline with maternal age. Conclusions Increased DSBs and reduced DNA repair in granulosa cells may contribute to ovarian aging. Discovery of therapeutics that targets these pathways might help maintain follicle reserve and postpone ovarian dysfunction with age.