ArrayExpress Uploader0mousecontrol siRNAcontrol siRNANcl siRNA #1Ncl siRNA #1Ncl siRNA #2Ncl siRNA #27340arrayexpress_sid6Despite RNAi-based screens to uncover genes controlling embryonic stem cell (ESC) identity, the pluripotency network remains poorly...E-GEOD-47872/profile/8773/arrayexpressuploader16cellembryonic stem cellstem cellDec.12, 2014Falseintegrated-analysis-identifies-key-determinants-ofE-GEOD-47872_A-AFFY-45Integrated analysis identifies key determinants of embryonic stem cell identity and homeostasisNov.12, 2014Despite RNAi-based screens to uncover genes controlling embryonic stem cell (ESC) identity, the pluripotency network remains poorly characterized, as does the precise molecular mechanisms underlying the balance between self-renewal and differentiation. Here we carried out a systematic meta-analysis of published gene expression data to rank-order genes based on their likelihood of regulating ESC identity. Not only did our analysis correctly rank known pluripotency-associated genes atop the list, but it also helped unearth many novel determinants of ESC identity including several components of functionally distinct complexes, as determined using RNAi. We focus on our top-hit Nucleolin, and characterize its mechanistic role in the maintenance of ESC homeostasis by shielding from differentiation-inducing redox imbalance-induced oxidative stress. Notably, we identify a conceptually novel mechanism involving a Nucleolin-dependent bistable switch regulating the homeostatic balance between self-renewal and differentiation in ESCs. Our gene ranks represent a rich and valuable resource for uncovering novel ESC regulators. Microarray gene expression profiling in E14Tg2a mESCs after transfection with indicated siRNAs: Ncl siRNA #1 (Invitrogen, 17975-MSS206961) Ncl siRNA #2 (Invitrogen, 17975-MSS275939), and Control siRNA duplex targeting firefly luciferase.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-47872http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-47872/samples/