Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs

Autor: Nicholas E. Banovich, Yoav Gilad, Bryan J Pavlovic, Courtney K Burrows, Irene Gallego Romero, Jonathan K. Pritchard, Kristen M. Patterson
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Epigenomics
Cancer Research
Somatic cell
Cellular differentiation
Biochemistry
Animal Cells
Medicine and Health Sciences
Induced pluripotent stem cell
Genetics (clinical)
Pathology and laboratory medicine
Connective Tissue Cells
Genetics
Regulation of gene expression
Staining
DNA methylation
Stem Cells
Cell Differentiation
Medical microbiology
Chromatin
3. Good health
Nucleic acids
Connective Tissue
Viruses
Epigenetics
Cellular Types
Anatomy
Pathogens
DNA modification
Chromatin modification
Research Article
Chromosome biology
Pluripotency
Cell biology
Herpesviruses
lcsh:QH426-470
Cell Potency
Induced Pluripotent Stem Cells
Biology
Research and Analysis Methods
Microbiology
03 medical and health sciences
Epstein-Barr virus
Humans
Molecular Biology
Cytoplasmic Staining
Ecology
Evolution
Behavior and Systematics
Biology and life sciences
Organisms
Viral pathogens
DNA
Fibroblasts
Human genetics
Microbial pathogens
lcsh:Genetics
030104 developmental biology
Biological Tissue
Genetic Loci
Specimen Preparation and Treatment
Gene expression
DNA viruses
Zdroj: PLoS Genetics
PLoS Genetics, Vol 12, Iss 1, p e1005793 (2016)
ISSN: 1553-7404
1553-7390
Popis: The advent of induced pluripotent stem cells (iPSCs) revolutionized human genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We find a remarkably small number of differences in DNA methylation and gene expression levels between iPSCs derived from different somatic precursors. Instead, we demonstrate genetic variation is associated with the majority of identifiable variation in DNA methylation and gene expression levels. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs, and that genetic variation is the main driver of regulatory differences between iPSCs of different donors. Our findings suggest that studies using iPSCs should focus on additional individuals rather than clones from the same individual.
Author Summary Induced pluripotent stem cells (iPSCs) are a new and powerful cell type that provides scientists the ability to model complex human diseases in vitro. These cells can be cryopreserved and later expanded, providing a renewable source of cells from the same individual. iPSCs can be made from a variety of somatic cells in the body and many labs have created them from blood and skin cells. We asked whether the cell type of origin impacts methylation and gene expression patterns in the reprogrammed iPSCs. Our findings indicate that there are remarkably few regulatory remnants of the cell type of origin in the iPSCs. In other words, most of the variation between iPSCs can be attributed to individual genetics. Our findings suggest that studies using iPSCs should focus on obtaining additional individuals rather than additional clones from the same individual. We caution that our current findings are limited to iPSCs and further studies are needed to address the question of somatic memory in differentiated cell types.
Databáze: OpenAIRE
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