Abstract:
:It is well known that human embryonic stem cells (hESCs) frequently acquire recurrent chromosomal abnormalities, very reminiscent of those found in cancerous cells. Given the parallels between cancer and stem cell biology, we set out to investigate the occurrence of a common form of genome instability in tumors, namely microsatellite instability (MSI), in hESCs. MSI is caused by a deficiency in mismatch repair (MMR) genes, which leads to the accumulation of mutations during DNA replication. In this study, we analyzed up to 122 microsatellites in a total of 10 hESC lines, for 1-11 different passages, ranging from passage 7 to passage 334. In two lines, this revealed that two microsatellites had altered allelic patterns. Small-pool PCR for several microsatellites and testing of the Bethesda panel microsatellites (commonly used in cancer studies) revealed that, whilst MSI is common in all tested lines, it occurs at a very low and variable frequency, ranging from ∼1 to 20% of the total number of alleles. In cancerous cells, MSI leads to multiple large shifts in allele sizes within the majority of the cells, while hESCs show small changes in a minority of the cells. Since these genetic alterations do not consistently take over the culture, we assume that they are not concurrent with a selective advantage as it is in tumors. Finally, the MMR genes showed a very variable gene expression that could not be correlated with the variable (low) levels of MSI in the different hESC lines.
journal_name
Mol Hum Reprodjournal_title
Molecular human reproductionauthors
Nguyen HT,Markouli C,Geens M,Barbé L,Sermon K,Spits Cdoi
10.1093/molehr/gau059subject
Has Abstractpub_date
2014-10-01 00:00:00pages
981-9issue
10eissn
1360-9947issn
1460-2407pii
gau059journal_volume
20pub_type
杂志文章abstract::Oocyte vitrification has been introduced into clinical settings without extensive pre-clinical safety testing. In this study, we analysed major safety aspects of human oocyte vitrification in a high security closed system: (i) chromosomal meiotic segregation, (ii) embryonic developmental kinetics and (iii) DNA (hydrox...
journal_title:Molecular human reproduction
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pub_type: 杂志文章
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更新日期:2010-09-01 00:00:00
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更新日期:2015-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2001-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2014-02-01 00:00:00
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更新日期:2011-07-01 00:00:00
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更新日期:1996-01-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gah198
更新日期:2005-08-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gag024
更新日期:2003-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2004-05-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Molecular human reproduction
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更新日期:2011-05-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
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更新日期:2001-07-01 00:00:00
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更新日期:1998-02-01 00:00:00
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journal_title:Molecular human reproduction
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更新日期:2009-05-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
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更新日期:2009-06-01 00:00:00
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更新日期:2006-10-01 00:00:00
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