NR2F1 regulates coding and noncoding transcriptome essential for spermatogonia establishment and maintenance [ChIP-seq]

Here, we reported NR2F1, a transcription factor starting its expression in fetal testis, is indispensable during mammalian spermatogonia development. Conditional knockout of Nr2f1 led to the loss of mouse pro-spermatogonia, impaired spermatogenesis and finally resulted in male infertility.

Using human spermatogonial stem cells (hSSCs) in vitro differentiation system, we demonstrated that NR2F1 not only regulate expression of several prominent spermatogonia protein-coding genes, but also regulate a subset of lncRNAs associated with chromatin remodeling. Deletion of NR2F1 impaired hSSCs proliferation rate and induced abnormal histone modification level at specific genomic loci. Three mutations are identified at the N-terminal of NR2F1 in non-obstructive azoospermia (NOA) patients and co-immunoprecipitation analyses revealed that these mutant NR2F1 fail to recruit co-factors involved in transcription initiation, thus impairing spermatogonia development.