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Human ES cells reveal recurrent genomic instability at 20q11.21

ABSTRACT: By analyzing five human embryonic stem (hES) cell lines over long-term culture, we detected a recurrent genomic instability in the human genome. An amplification of 2.5–4.6 Mb at 20q11.21, encompassing about 23 genes in common, appeared in four cell lines of different origins. This amplification, which has been associated with oncogenic transformation, may provide a selective advantage to hES cells in culture

ORGANISM(S): Homo sapiens

PROVIDER: GSE13565 | GEO | 2008/11/19

SECONDARY ACCESSION(S): PRJNA110665

REPOSITORIES: GEO

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Human ES cells reveal recurrent genomic instability at 20q11.21

Project description:By analyzing five human embryonic stem (hES) cell lines over long-term culture, we detected a recurrent genomic instability in the human genome. An amplification of 2.5â4.6 Mb at 20q11.21, encompassing about 23 genes in common, appeared in four cell lines of different origins. This amplification, which has been associated with oncogenic transformation, may provide a selective advantage to hES cells in culture Array-based comparative genomic hybridization, was performed on genomic DNA samples from different human embryonic stem cell lines, all cultured in our laboratory under the same conditions. VUB05-HD is an hES cell line carrying the Huntingtin mutant gene H1, H9, SA01, and VUB01 are various hES cell lines GSM341552 and GSM341553: SNP analysis GSM341589 to GSM341669: CGH analysis

2010-05-16 | E-GEOD-13565 | biostudies-arrayexpress

Gain of 20q11.21 in human pluripotent stem cells impairs TGFβ-dependent ectodermal commitment

Project description:Altered TGFb signaling in lines with a 20q11.21 amplification has a dramatic negative effect on ectodermal differentiation

2019-06-12 | GSE116372 | GEO

Characterization of human embryonic stem cells with features of neoplastic progression

2008-12-25 | GSE13995 | GEO

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

Project description:The International Stem Cell Initiative analyzed 127 human embryonic stem cell lines and 11 induced pluripotent cell lines, from 39 laboratories worldwide for genetic changes occurring during culture. Most cell lines were analyzed at an early and late passage. Population structure analysis from SNP detection revealed that the cell lines included representatives of all major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed but haphazardly with no link to time in culture. Structural variants (SVs), below the level of standard chromosome banding, determined from the SNP arrays, also appeared sporadically but no common variants related to culture were observed on chromosomes 1, 12 and 17. However, overlapping SV gains acquired in the chromosome 20q11.21 region during extended culture were identified in over 20% of the cell lines. Three genes within the minimal shared region, ID1, BCL2L1, and HM13, are expressed in human ES cells, with BCL2L1 a strong candidate for driving this culture adaptation of ES cells.

2011-11-12 | GSE33522 | GEO

Comparable mRNA expression of pluripotency-related genes in SNUhES3 cells cultured on autofeeder or xenofeeder system

Project description:I developed a new culture system for hES cells; this system does not require supplementation with bFGF to obtain hES cells that are suitable for tissue engineering and regenerative medicine. This culture system employed mesenchymal stem cells derived from hES cells (hESC-MSCs) as autologous human feeder cells in the absence of bFGF. For pluripotency-related gene expression profiling, a cDNA microarray analysis was performed

2011-02-02 | GSE26993 | GEO

TPX2 Amplification-Driven Aberrant Mitosis in Long-Term Cultured Human Embryonic Stem Cells

Project description:Although human embryonic stem cells (hESCs) are equipped with highly effective machinery for the maintenance of genome integrity, the frequency of genetic aberrations during long-term in vitro hESC culture has been a serious issue that raises concerns over their safety in future clinical applications. By passaging hESCs over a broad range of timepoints, we found that mitotic aberrations, such as the delay of mitosis, multipolar centrosomes, and chromosome mis-segregation, were increased in the late-passaged hESCs (LP-hESCs) in parallel with polyploidy compared to early-passaged hESCs (EP-hESCs). Through high-resolution genome-wide approaches and by following transcriptome analysis, we found that LP-hESCs with a minimal amplicon in chromosome 20q11.21 highly expressed TPX2 (targeting protein for Xklp2), a key protein for governing spindle assembly and cancer malignancy. Consistent with these findings, the inducible expression of TPX2 in EP-hESCs reproduced aberrant mitotic events, such as the delay of mitotic progression, spindle stability, misaligned chromosomes, and polyploidy. This data suggests that the amplification and increased transcription of the TPX2 gene at 20q11.21 could contribute to an increase in aberrant mitosis due to altered spindle dynamics.

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Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

Project description:array-CGH analysis of human neural stem cells derived from human ES cells during long term in vitro culture

2012-01-25 | GSE33708 | GEO

Characterization of human embryonic stem cells with features of neoplastic progression

Project description:Cultured human embryonic stem (hES) cells can acquire genetic and epigenetic changes that make them vulnerable to transformation. As hES cells with cancer-cell characteristics share properties with normal hES cells, such as self-renewal, teratoma formation and the expression of pluripotency markers, they may be misconstrued as superior hES cells with enhanced âstemnessâ. We characterize two variant hES cell lines (v-hESC-1 and v-hESC-2) that express pluripotency markers at high levels and do not harbor chromosomal abnormalities by standard cytogenetic measures. We show that the two lines possess some features of neoplastic progression, including a high proliferative capacity, growth-factor independence, a 9- to 20-fold increase in frequency of tumor initiating cells, niche independence and aberrant lineage specification, although they are not malignant. Array comparative genomic hybridization revealed an amplification at 20q11.1-11.2 in v-hESC-1 and a deletion at 5q34a-5q34b;5q3 and a mosaic gain of chromosome 12 in v-hESC-2. These results emphasize the need for functional characterization to distinguish partially transformed and normal hES cells. Custom oligonucleotide array gene expression analysis was performed on total RNA from low passage normal and variant human embryonic stem cell (hESC) lines, all cultured in our laboratory under the same conditions. Furthermore, array-based comparative genomic hybridization was also performed on the normal and variant hESC lines. v-hESC-1 and v-hESC-2 represent two independent lines that display neoplastic characteristics with distinctive copy number alterations. v-hESC-1_A2B5 represents neural precursor cultures differentiated from variant hES cells. GSM349016-GSM349022: Gene expression analysis GSM351500-GSM351511: aCGH analysis

2010-06-24 | E-GEOD-13995 | biostudies-arrayexpress

Gene expression comparison between human embryonic stem cell lines with a normal karyotype and after acquiring a duplication of 20q11.21

Project description:Since the introduction of high-resolution molecular cytogenetic methods for the screening for chromosomal abnormalities in human embryonic stem cells (hESC), numerous laboratories worldwide have reported the gain of 20q11.21 as a recurrent mutation. Recently, in a large joint study, the International Stem Cell Initiative (ISCI) screened 125 hESC lines worldwide and found this aberration in over 20% of the lines. In our laboratory, we found an increased copy number of 20q11.21 in four hESC lines, VUB01, VUB02, VUB03 and VUB07. We first carried out Affymetrix HG-U133-Plus2 gene-expression microarray analysis of pairs of the mutant and wild type sublines. We identified a small group of very significantly deregulated genes, but none of them were located in the region of duplication. Validation of these results by qRT-PCR revealed that CHCHD2 and TRPC6 were most consistently deregulated.

2019-06-12 | GSE41439 | GEO

Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

Project description:array-CGH analysis of human neural stem cells derived from human ES cells during long term in vitro culture array-CGH analysis of human neural stem cells derived from human ES cells comparing control genomic DNA

2012-01-25 | E-GEOD-33708 | biostudies-arrayexpress

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