Objectives Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder. Insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) serves as an HMGA2 target gene to promote the proliferation of granulosa cells (GCs). However, it is still unclear whether IGF2BP2 participates in the pathogenesis of PCOS as RNA binding protein (RBP). In this study, we aimed to elucidate IGF2BP2‐interacting transcripts, global transcriptome together with alternative splicing in GCs to eventually uncover potential mechanisms of PCOS pathogenesis. Materials and Methods The expression of IGF2BP2 in GCs from PCOS patients was detected using quantitative reverse transcription PCR (RT‐qPCR) and western blot. We captured IGF2BP2‐interacting transcripts, global transcriptome together with alternative splicing by RNA immunoprecipitation sequencing (RIP‐seq) and RNA sequencing (RNA‐seq). KGN cells transfected with IGF2BP2 overexpressing plasmids and nuclear factor 1 C‐type (NFIC) siRNAs, were applied to CCK‐8, EdU and TUNEL assays. Results IGF2BP2 was highly expressed in GCs from PCOS patients. As an RBP, it preferentially bound to the 3′and 5′UTRs of mRNAs with GGAC motif and a newly found GAAG motif. The overexpression of IGF2BP2 changed the transcriptome profile of KGN cells. IGF2BP2 functioned to regulate alternative splicing events and promote cell proliferation through inhibiting exon skipping events of NFIC. Conclusion In conclusion, we demonstrated that IGF2BP2 promotes GC proliferation via regulating alternative splicing of NFIC in PCOS. The findings help to better understand the roles of IGF2BP2 in the pathogenesis of PCOS.
The placenta is one of the most important yet least understood organs. Due to the limitations of conventional research approaches, we are still far from a comprehensive understanding of mouse placentation, especially regarding the differentiation of trophoblast lineages at the early developmental stage. To decipher cell compositions and developmental processes, we systematically profile the single-cell transcriptomes of trophoblast cells from extraembryonic tissues (embryonic day 7.5 (E7.5) and E8.5) and placentae (E9.5–E14.5) at one-day intervals. We identify distinct trophoblast cell types during mouse placentation, including unreported progenitor cells and intermediate precursor cells. An updated differentiation roadmap of mouse trophoblast lineages is presented following systematic transcriptome analyses. Based on transcriptomic regulatory network inference, we specify transcription factors responsible for the regulation of dynamic developmental processes during lineage diversification. We map lineage differentiation trajectories and find that sinusoid trophoblast giant cells arise from the subpopulation of ectoplacental cone cells. We provide a comprehensive single-cell data resource to shed light on future mechanistic studies of the gene regulatory networks governing hemochorial placentation.
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