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

Kurt Jacobs; Afroditi Mertzanidou; Mieke Geens; Ha Nguyen Thi; Catherine Staessen; Claudia Spits

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

Kurt Jacobs, Afroditi Mertzanidou, Mieke Geens, Ha Nguyen Thi, Catherine Staessen, Claudia Spits

Department of Embryology and Genetics

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1-10
Number of pages	10
Journal	Nature Communications
Volume	5
Issue number	4227
Publication status	Published - 27 Jun 2014

Keywords

Embryonic Stem Cells
Chromosomal Instability
Copy Number Variation

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http://www.nature.com/ncomms/2014/140627/ncomms5227/full/ncomms5227.html?message-global=remove

FWOAL535: Chromosomal abnormalities in human preimplantation embryos and embryonic stem cells: causes, mechanisms and consequences for IVF and regenerative medicine
Sermon, K., Spits, C., Van De Velde, H., Liebaers, I., Jacobs, K. & Staessens, C.
1/01/10 → 31/12/13
Project: Fundamental

Cite this

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title = "Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations",

abstract = "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.",

keywords = "Embryonic Stem Cells, Chromosomal Instability, Copy Number Variation",

author = "Kurt Jacobs and Afroditi Mertzanidou and Mieke Geens and {Nguyen Thi}, Ha and Catherine Staessen and Claudia Spits",

year = "2014",

month = jun,

day = "27",

language = "English",

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pages = "1--10",

journal = "Nature Communications",

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T1 - Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations

AU - Jacobs, Kurt

AU - Mertzanidou, Afroditi

AU - Geens, Mieke

AU - Nguyen Thi, Ha

AU - Staessen, Catherine

AU - Spits, Claudia

PY - 2014/6/27

Y1 - 2014/6/27

N2 - 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.

AB - 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.

KW - Embryonic Stem Cells

KW - Chromosomal Instability

KW - Copy Number Variation

M3 - Article

VL - 5

SP - 1

EP - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 4227

ER -

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

Abstract

Keywords

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Projects

FWOAL535: Chromosomal abnormalities in human preimplantation embryos and embryonic stem cells: causes, mechanisms and consequences for IVF and regenerative medicine

Cite this