title: SON connects the splicing-regulatory network with pluripotency in human embryonic stem cells.
abstract: Human embryonic stem cells (hESCs) harbour the ability to undergo lineage-specific differentiation into clinically relevant cell types. Transcription factors and epigenetic modifiers are known to play important roles in the maintenance of pluripotency of hESCs. However, little is known about regulation of pluripotency through splicing. In this study, we identify the spliceosome-associated factor SON as a factor essential for the maintenance of hESCs. Depletion of SON in hESCs results in the loss of pluripotency and cell death. Using genome-wide RNA profiling, we identified transcripts that are regulated by SON. Importantly, we confirmed that SON regulates the proper splicing of transcripts encoding for pluripotency regulators such as OCT4, PRDM14, E4F1 and MED24. Furthermore, we show that SON is bound to these transcripts in vivo. In summary, we connect a splicing-regulatory network for accurate transcript production to the maintenance of pluripotency and self-renewal of hESCs.
authors.affiliation: Gene Regulation Laboratory, Genome Institute of Singapore, 138672, Singapore.|Department of Biological Sciences, National University of Singapore, 117543, Singapore.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Lu
authors.affiliation: Gene Regulation Laboratory, Genome Institute of Singapore, 138672, Singapore.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Göke
authors.affiliation: Gene Regulation Laboratory, Genome Institute of Singapore, 138672, Singapore.|Department of Biochemistry, National University of Singapore, 117597, Singapore.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Sachs
authors.affiliation: Department of Biology, Université de Sherbrooke, 2500 boulevard de l'Université Sherbrooke, Québec J1K 2R1, Canada.
authors.forename: Pierre-Étienne
authors.initials: PÉ
authors.lastname: Jacques
authors.affiliation: Gene Regulation Laboratory, Genome Institute of Singapore, 138672, Singapore.
authors.forename: Hongqing
authors.initials: H
authors.lastname: Liang
authors.affiliation: School of Biomedical Sciences, Lo Kwee Seong Integrated Biomedical Sciences Building, Chinese University of Hong Kong, Hong Kong 999077, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: McGill University & Genome Quebec Innovation Center, 740 Dr Penfield Avenue, Montréal, Québec H3A 1A4, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bourque
authors.affiliation: Department of Biological Sciences, Wright State University, Dayton, Ohio 45435, USA.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Bubulya
authors.affiliation: Gene Regulation Laboratory, Genome Institute of Singapore, 138672, Singapore.|Department of Biological Sciences, National University of Singapore, 117543, Singapore.|Department of Biochemistry, National University of Singapore, 117597, Singapore.|Graduate School for Integrative Sciences & Engineering, National University of Singapore, 117456, Singapore.|School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
authors.forename: Huck-Hui
authors.initials: HH
authors.lastname: Ng
mesh_terms: D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D015778:Minor Histocompatibility Antigens; D011485:Protein Binding; D012326:RNA Splicing / Q000502:physiology*; D059467:Transcriptome
chemical_list: D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; C088203:SON protein, human