Genetic and epigenetic stability of human pluripotent stem cells

Lund, Riikka; Närvä, Elisa; Lahesmaa, Riitta

doi:10.1038/nrg3271

Cited by 223 publications

(170 citation statements)

References 108 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…More recently, the group of Abyzov et al 6 made use of the clonal nature of humaninduced pluripotent stem cells (hiPSCs) to show that human skin fibroblasts are highly mosaic, with up to 30% of cells carrying copy number variants (CNVs). In the field of human pluripotent stem cell research, a large number of studies have shown that human embryonic stem cell (hESC) cultures are frequently taken over by chromosomally abnormal cells 7,8 , most probably because of a selective advantage caused by the chromosomal aberration 9,10 . Conversely, not much is known on how frequently hESC spontaneously mutate, either through abnormal chromosome segregation or by acquiring small amplifications or deletions, nor on the nature of these changes.…”

mentioning

confidence: 99%

“…In recent years, many groups have performed high-resolution screening of somatic cell populations 1,6,11,12 as well as hiPSC and hESC 7,8 and have reported de novo CNVs ranging from 10 kb to several Mb. It is important to bear in mind that these studies are based on the analysis of DNA from extractions from large numbers of cells, which only allows detection of CNVs if they are present in at least 5-10% of the cells 11,12 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2014

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

show abstract

“…This will probably be achieved given time and effort, but many of the non-physiologic conditions taken over from traditional cell culture techniques contribute to the problems. Originally hPSC cultures were thought to be genetically stable, but we have lately learnt about their limitations in this respect (Mitalipova et al, 2005;Lund et al, 2012;Steinemann et al, 2013). Other limitations are costs of culture and complex differentiation protocols, which may require months of labor, media, and supplements.…”

Section: The Genesis Of Gccp 10mentioning

confidence: 99%

Good Cell Culture Practice for stem cells and stem-cell-derived models

Pamies

Bal‐Price

Simeonov

et al. 2016

ALTEX

138

View full text Add to dashboard Cite

SummaryThe first guidance on Good Cell Culture Practice (GCCP) dates back to 2005. This document expands this to include aspects of quality assurance for in vitro cell culture focusing on the increasingly diverse cell types and culture formats used in research, product development, testing and manufacture of biotechnology products and cell-based medicines. It provides a set of basic principles of best practice that can be used in training new personnel, reviewing and improving local procedures, and helping to assure standard practices and conditions for the comparison of data between laboratories and experimentation performed at different times. This includes recommendations for the documentation and reporting of culture conditions. It is intended as guidance to facilitate the generation of reliable data from cell culture systems, and is not intended to conflict with local or higher level legislation or regulatory requirements. It may not be possible to meet all recommendations in this guidance for practical, legal or other reasons. However, when it is necessary to divert from the principles of GCCP, the risk of decreasing the quality of work and the safety of laboratory staff should be addressed and any conclusions or alternative approaches justified. This workshop report is considered a first step toward a revised GCCP 2.0.

show abstract

“…This is probably only a matter of time, but many of the non-physiological conditions from traditional cell cultures contribute here. Stem cells have been praised for their genetic stability, which appears to be better than for other cell lines, but we have increasingly discovered their limitations in that respect, too (Mitalipova et al, 2005;Lund et al, 2012;Steinemann et al, 2013). The limitations experienced first are costs of culture and slow growth -many protocols require months, and labour, media, and supplement costs add up.…”

mentioning

confidence: 99%

Evolution of toxicological science: the need for change

Hartung

2017

IJRAM

View full text Add to dashboard Cite

Evolution requires change but the field of toxicology has not kept pace. The top ten problems urging change are: 1) disparity of testing requirements and risk acceptance for different products and geographical areas; 2) throughput and testing costs versus testing needs; 3) limited predictivity for humans; 4) precautionary approaches from drug development adapted to other areas; 5) animal use; 6) traditional tests unsuitable for new products; 7) lack of coverage for new hazards; 8) failure to address mixtures of toxicants; 9) lack of coverage for individual susceptibilities and vulnerable subpopulations; 10) poor basic research and publication standards. The intransigence at the root of these problems is discussed with reference to current international toxicological policies and methods. For each, the limitations are reviewed with reference to key literature. While current approaches are still needed, there is room for substantial change. To meet the challenges of the 21st century, revolution rather than evolution is required.

show abstract

Genetic and epigenetic stability of human pluripotent stem cells

Cited by 223 publications

References 108 publications

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

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

Good Cell Culture Practice for stem cells and stem-cell-derived models

Evolution of toxicological science: the need for change

Contact Info

Product

Resources

About