Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations

Current knowledge on chromosomal mosaicism in human cell cultures is mostly based on cytogenetic banding methods. The recent development of high-resolution full-genome analysis methods applicable to single cells is providing new insights into genetic and cellular diversity. Here we study the genetic...

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Veröffentlicht in:Nature communications 2014-06, Vol.5 (1), p.4227-4227, Article 4227
Hauptverfasser: Jacobs, Kurt, Mertzanidou, Afroditi, Geens, Mieke, Thi Nguyen, Ha, Staessen, Catherine, Spits, Claudia
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container_issue 1
container_start_page 4227
container_title Nature communications
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creator Jacobs, Kurt
Mertzanidou, Afroditi
Geens, Mieke
Thi Nguyen, Ha
Staessen, Catherine
Spits, Claudia
description Current knowledge on chromosomal mosaicism in human cell cultures is mostly based on cytogenetic banding methods. The recent development of high-resolution full-genome analysis methods applicable to single cells is providing new insights into genetic and cellular diversity. Here we study the genetic content of 92 individual human cells, including fibroblasts, amniocytes and embryonic stem cells (hESCs), using single-cell array-based comparative genomic hybridization (aCGH). We find that human somatic and embryonic stem cell cultures show significant fractions of cells carrying unique megabase-scale chromosomal abnormalities, forming genetic mosaics that could not have been detected by conventional cytogenetic methods. These findings are confirmed by studying seven clonal hESC sub-lines by aCGH. Furthermore, fluorescent in situ hybridisation reveals an increased instability of the subtelomeric regions in hESC as compared to somatic cells. This genetic heterogeneity may have an impact on experimental results and, in the case of hESC, on their potential clinical use. De novo copy number variations are known to occur in somatic cell populations and pluripotent stem cells. Here the authors use single-cell array comparative genomic hybridization to identify copy number variations in individual human somatic and embryonic stem cells.
doi_str_mv 10.1038/ncomms5227
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subjects 13/100
14/32
631/136/532/2117
631/208/2489/1381/1661
Amnion - cytology
Amnion - metabolism
Arrays
Cell culture
Cell Line
Cells, Cultured
Chromosomes
Chromosomes, Human - genetics
Comparative Genomic Hybridization
Embryonic Stem Cells - metabolism
Fibroblasts - metabolism
Humanities and Social Sciences
Humans
Hybridization
In Situ Hybridization, Fluorescence
Mosaicism
multidisciplinary
Science
Science (multidisciplinary)
Stem cells
title Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations
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