Embryonic Stem Cells

Using genetic diversity to understand pluripotency and cell fate decisions
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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.