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The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines.

Canham MA, Van Deusen A, Brison DR, De Sousa PA, Downie J, Devito L, Hewitt ZA, Ilic D, Kimber SJ, Moore HD, Murray H, Kunath T - Sci Rep (2015)

Bottom Line: The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality.A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation.In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, UK.

ABSTRACT
The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality. Although the vast majority of hESC lines have been derived for research purposes only, about 50 lines have been established under Good Manufacturing Practice (GMP) conditions. Cell types differentiated from these designated lines may be used as a cell therapy to treat macular degeneration, Parkinson's, Huntington's, diabetes, osteoarthritis and other degenerative conditions. It is essential to know the genetic stability of the hESC lines before progressing to clinical trials. We evaluated the molecular karyotype of 25 clinical-grade hESC lines by whole-genome single nucleotide polymorphism (SNP) array analysis. A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation. In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture. The large number of available clinical-grade hESC lines with defined molecular karyotypes provides a substantial starting platform from which the development of pre-clinical and clinical trials in regenerative medicine can be realised.

No MeSH data available.


Related in: MedlinePlus

An identical duplication found in sibling KCL hESC lines, but not present on the DGV.Chromosome 5 ideograms from SNP array analysis of KCL032 and KCL033 hESC lines with the common CNV indicated by blue arrows. This 2.4 Mb duplication on chromosome 5p14.3 included the CDH18 gene. A duplication of this size was not present on the DGV, but a smaller duplication (nsv597424) covering most of the CDH18 exons was present, and a number of smaller deletions have been observed in this region. Only published CNVs greater than 100 kb are represented here.
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f4: An identical duplication found in sibling KCL hESC lines, but not present on the DGV.Chromosome 5 ideograms from SNP array analysis of KCL032 and KCL033 hESC lines with the common CNV indicated by blue arrows. This 2.4 Mb duplication on chromosome 5p14.3 included the CDH18 gene. A duplication of this size was not present on the DGV, but a smaller duplication (nsv597424) covering most of the CDH18 exons was present, and a number of smaller deletions have been observed in this region. Only published CNVs greater than 100 kb are represented here.

Mentions: We identified a novel 2.4 Mb gain on chromosome 5p14.3, containing a single gene, Cadherin-18, that was present in two sibling cell lines, KCL032 and KCL033 (Fig. 4), but not in KCL034, a third sibling line2058. A duplication of this size has not been reported to date, but its presence in two sibling hESC lines strongly suggests it was inherited from one of the parents of the donated blastocysts rather than by acquisition of an identical CNV during hESC derivation and culture.


The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines.

Canham MA, Van Deusen A, Brison DR, De Sousa PA, Downie J, Devito L, Hewitt ZA, Ilic D, Kimber SJ, Moore HD, Murray H, Kunath T - Sci Rep (2015)

An identical duplication found in sibling KCL hESC lines, but not present on the DGV.Chromosome 5 ideograms from SNP array analysis of KCL032 and KCL033 hESC lines with the common CNV indicated by blue arrows. This 2.4 Mb duplication on chromosome 5p14.3 included the CDH18 gene. A duplication of this size was not present on the DGV, but a smaller duplication (nsv597424) covering most of the CDH18 exons was present, and a number of smaller deletions have been observed in this region. Only published CNVs greater than 100 kb are represented here.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660465&req=5

f4: An identical duplication found in sibling KCL hESC lines, but not present on the DGV.Chromosome 5 ideograms from SNP array analysis of KCL032 and KCL033 hESC lines with the common CNV indicated by blue arrows. This 2.4 Mb duplication on chromosome 5p14.3 included the CDH18 gene. A duplication of this size was not present on the DGV, but a smaller duplication (nsv597424) covering most of the CDH18 exons was present, and a number of smaller deletions have been observed in this region. Only published CNVs greater than 100 kb are represented here.
Mentions: We identified a novel 2.4 Mb gain on chromosome 5p14.3, containing a single gene, Cadherin-18, that was present in two sibling cell lines, KCL032 and KCL033 (Fig. 4), but not in KCL034, a third sibling line2058. A duplication of this size has not been reported to date, but its presence in two sibling hESC lines strongly suggests it was inherited from one of the parents of the donated blastocysts rather than by acquisition of an identical CNV during hESC derivation and culture.

Bottom Line: The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality.A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation.In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, UK.

ABSTRACT
The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality. Although the vast majority of hESC lines have been derived for research purposes only, about 50 lines have been established under Good Manufacturing Practice (GMP) conditions. Cell types differentiated from these designated lines may be used as a cell therapy to treat macular degeneration, Parkinson's, Huntington's, diabetes, osteoarthritis and other degenerative conditions. It is essential to know the genetic stability of the hESC lines before progressing to clinical trials. We evaluated the molecular karyotype of 25 clinical-grade hESC lines by whole-genome single nucleotide polymorphism (SNP) array analysis. A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation. In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture. The large number of available clinical-grade hESC lines with defined molecular karyotypes provides a substantial starting platform from which the development of pre-clinical and clinical trials in regenerative medicine can be realised.

No MeSH data available.


Related in: MedlinePlus