The Involvement Of A Long Non-coding RNA In Self-renewal Of Mouse Spermatogonial Stem Cells

In the adult body of mammal,several self-renewing systems exist,including hematopoiesis,spermatogenesis,intestinal epithelium,and skin,but only spermato-genesis is responsible for generation of the male gamete and contributes to the genetic diversity necessary for evolution.Spermatogonial stem cells(SSCs)are essential to maintaining male fertility and species continuity,Providing the foundation for spermatogenesis.Although SSCs represent a small fraction of the testicular cell population(i.e.,only approximately 1 in 3000 adult testis cells is stem cell in the mouse testis),they are one of the most productive and biologically active adult stem cells.This feature makes SSCs an excellent model to study biological processes regulating adult stem cell self-renewal and differentiation.Insight regarding mechanisms controlling gene expression in the spermatogonial stem cell(SSC)will improve our understanding of the proeesses regulating spermatogenesis and aid in treating problems associated with male infertility.Eukaryotic transcriptomes have been shown to be extremely complex.The discovery of noncoding RNAs has expanded our view of gene expression and protein synthesis.Recently,long noncoding RNAs(IncRNAs,longer than 200 nucleotides)have been identified as key regulators of stem cell fate;but their role in SSCs has not been explored.Here,we report that a novel spermatogonia.specific IncRNA(lncRNA033862)is essential for the survival of murine SSCs.LncRNA033862 is expressed in early spermatogonia including SSC and was among 805 IncRNAs identified by global expression profiling as responsive to glial cell-derived neurotrophic factor(GDNF),a growth factor required for SSC self-renewal.LncRNA033862 1s an antisense transcript of the GDNF receptor alphal(Gfr?1)that lacks protein coding potential and regulates Gfr?1 expression levels by interacting with Gfr?1 chromatin.Importantly,lncRNA033862 knockdown severely impairs SSC survival and their capacity to repopulate recipient testes in a transplantation assay.Collectively,our data provide the first evidence that long non-coding RNA regulates SSCs fate.