Functions and mechanisms of circular RNAs in regulating stem cell differentiation.

ABSTRACT

Stem cells are a class of undifferentiated cells with great self-renewal and differentiation capabilities that can differentiate into mature cells in specific tissue types. Stem cell differentiation plays critical roles in body homoeostasis, injury repair and tissue generation. The important functions of stem cell differentiation have resulted in numerous studies focusing on the complex molecular mechanisms and various signalling pathways controlling stem cell differentiation. Circular RNAs (circRNAs) are a novel class of noncoding RNAs with a covalently closed structure present in eukaryotes. Numerous studies have highlighted important biological functions of circRNAs, and they play multiple regulatory roles in various physiological and pathological processes. Importantly, multiple lines of evidence have shown the abnormal expression of numerous circRNAs during stem cell differentiation, and some play a role in regulating stem cell differentiation, highlighting the role of circRNAs as novel biomarkers of stem cell differentiation and novel targets for stem cell-based therapy. In this review, we systematically summarize and discuss recent advances in our understanding of the roles and underlying mechanisms of circRNAs in modulating stem cell differentiation, thus providing guidance for future studies to investigate stem cell differentiation and stem cell-based therapy.Abbreviations CircRNAs circular RNAs; ESCs embryonic stem cells; ADSCs adipose-derived mesenchymal stem cells; ecircRNAs exonic circRNAs; EIciRNAs exon-intron circRNAs; eiRNAs circular intronic RNAs; tricRNAs tRNA intronic circRNAs; pol II polymerase II; snRNP small nuclear ribonucleoprotein; m6A N6-methyladenosine; AGO2 Argonaute 2; RBPs RNA-binding proteins; MBNL muscleblind-like protein 1; MSCs mesenchymal stem cells; hiPSCs human induced pluripotent stem cells; hiPSC-CMs hiPSC-derived cardiomyocytes; hBMSCs human bone marrow mesenchymal stem cells; hADSCs human adipose-derived mesenchymal stem cells; hDPSCs human dental pulp stem cells; RNA-seq high-throughput RNA sequencing; HSCs haematopoietic stem cells; NSCs neural stem cells; EpSCs epidermal stem cells; hESCs human embryonic stem cells; mESCs murine embryonic stem cells; MNs motor neurons; SSUP small subunit processome; BMSCs bone marrow-derived mesenchymal stem cells; OGN osteoglycin; GIOP glucocorticoid­induced osteoporosis; CDR1as cerebellar degeneration-related protein 1 transcript; SONFH steroid-induced osteogenesis of the femoral head; rBMSCs rat bone marrow-derived mesenchymal stem cells; QUE quercetin; AcvR1b activin A receptor type 1B; BSP bone sialoprotein; mADSCs mouse ADSCs; PTBP1 polypyrimidine tract-binding protein; ER endoplasmic reticulum; hUCMSCs MSCs derived from human umbilical cord; MSMSCs maxillary sinus membrane stem cells; SCAPs stem cells from the apical papilla; MyoD myogenic differentiation protein 1; MSTN myostatin; MEF2C myocyte enhancer factor 2C; BCLAF1 BCL2-associated transcription factor 1; EpSCs epidermal stem cells; ISCs intestinal stem cells; NSCs neural stem cells; Lgr5+ ISCs crypt base columnar cells; ILCs innate lymphoid cells.