Embryonic Stem Cells
Using genetic diversity to understand pluripotency and cell fate decisions
Systems genetics of ground state pluripotency in Diversity Outbred mESCs.
A. We map 6,589 variants that affect transcript abundance in DO mESC lines, including a single Chr 15 locus that modulates 254 genes associated with pluripotency (red band). B-C. Mediation identifies Lifr expression as the causal intermediate conferring this trans-effect. D. The strain allele effects at this locus on target gene expression show a 4:4 pattern, with NOD and the three wild-derived strains as one group. A single SNP within 20kb of Lifr matches this pattern, and is found in a region of open chromatin. E. Allele swap experiments with high and low Lifr expressing founder mESC lines in sensitized culture conditions validates this SNP as the causal variant.