a robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells一个健壮的方法识别组织基因表达调控变体使用个性化的人类诱导多能干细胞.pdfVIP

A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells 1. 2. 3 1 4 2 4 Je-Hyuk Lee *, In-Hyun Park , Yuan Gao , Jin Billy Li , Zhe Li , George Q. Daley , Kun Zhang , George M. Church1* 1 Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Division of Pediatric Hematology Oncology, Children’s Hospital Boston, Boston, Massachusetts, United States of America, 3 Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia, United States of America, 4 Department of Bioengineering, University of California San Diego, La Jolla, California, United States of America Abstract Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS) cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-c