A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells

Lee, J. H., Park, I. H., Gao, Y., Li, J. B., Li, Z., Daley, G. Q., Zhang, K., Church, G. M. (2009) A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells. PLoS Genet, 5 (11). e1000718. ISSN 1553-7404 (Electronic)1553-7390 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/19911041
DOI: 10.1371/journal.pgen.1000718

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-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

Item Type: Paper
Uncontrolled Keywords: Alleles Cell Differentiation Cell Line Cells, Cultured Cluster Analysis Computational Biology/ methods DNA, Complementary Flow Cytometry Gene Expression Regulation/ genetics Human Genome Project Humans Induced Pluripotent Stem Cells Nucleic Acid Amplification Techniques Organ Specificity Regulatory Elements, Transcriptional Reproducibility of Results
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:
Communities: CSHL labs > Lee lab
Depositing User: Matt Covey
Date Deposited: 22 Jul 2015 16:01
Last Modified: 22 Jul 2015 16:01
PMCID: PMC2766639
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31637

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