title: Aire promotes the self-renewal of embryonic stem cells through Lin28.
abstract: Abstract   Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells. We presented the first evidence that the let-7 microRNA family contributed to the self-renewal promoting effect of Aire on ES cells. Moreover, we showed that Aire and Lin28 are co-expressed in the genital ridge, oocytes, and cleavage-stage embryos, and the expression level of Lin28 is correlated with the expression level of Aire. Although it is widely considered to be a promiscuous gene expression activator, these results indicated that Aire promotes the self-renewal of ES cells through a specific pathway (i.e., the activation of Lin28 and the inhibition of the let-7 microRNA family). The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. This study presents the first molecular pathway that incorporates Aire into the pluripotency network. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. These functions reveal novel perspectives for studying the molecular mechanisms behind the establishment and sustenance of pluripotent identity.
authors.affiliation: Institute of Genetics, College of Life Sciences, Zhejiang University, Hangzhou, China .
authors.forename: Gu
authors.initials: G
authors.lastname: Bin
authors.forename: Zhang
authors.initials: Z
authors.lastname: Jiarong
authors.forename: Wang
authors.initials: W
authors.lastname: Shihao
authors.forename: Song
authors.initials: S
authors.lastname: Xiuli
authors.forename: Xu
authors.initials: X
authors.lastname: Cheng
authors.forename: Chen
authors.initials: C
authors.lastname: Liangbiao
authors.forename: Zhang
authors.initials: Z
authors.lastname: Ming
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D005854:Germ Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D000096927:AIRE Protein
chemical_list: D035683:MicroRNAs; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; C488352:Lin-28 protein, mouse; C542687:mirnlet7 microRNA, mouse