Chromosomal instability and aneuploidy in cancer: from yeast to man

Pfau, Sarah J.; Amon, Angelika

doi:10.1038/embor.2012.65

Cited by 195 publications

(172 citation statements)

References 116 publications

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“…Therefore, investigation of the pathways related to cell cycle control and DNA damage response will help to understand the process of hUC-MSC passaging and the molecular mechanisms underlying genomic stability. Because CNVs or chromosomal number change has been found in a wide variety of human neoplastic tumors, [38][39][40][41] the potential tumorigenicity of MSCs with chromosomal abnormalities or CNV mutations cannot be completely ruled out. As the occurrence of genetic alterations during in vitro cultivation was relatively high and pathway related, the development of optimized culture methods will also be needed to stabilize the genome of stem cells during long-term cultivation.…”

Section: Discussionmentioning

confidence: 99%

Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation

et al. 2014

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“…A ging and age-associated diseases are becoming the fastestgrowing area of epidemiology in most developed countries (1)(2)(3)(4). Identification of molecular mechanisms that lead to the development of interventions to delay the onset of age-associated diseases could have tremendous global impacts on public health (5).…”

Section: Saccharomyces Cerevisiaementioning

confidence: 99%

High-throughput analysis of yeast replicative aging using a microfluidic system

Liu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

156

174

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Saccharomyces cerevisiae has been an important model for studying the molecular mechanisms of aging in eukaryotic cells. However, the laborious and low-throughput methods of current yeast replicative lifespan assays limit their usefulness as a broad genetic screening platform for research on aging. We address this limitation by developing an efficient, high-throughput microfluidic single-cell analysis chip in combination with high-resolution time-lapse microscopy. This innovative design enables, to our knowledge for the first time, the determination of the yeast replicative lifespan in a highthroughput manner. Morphological and phenotypical changes during aging can also be monitored automatically with a much higher throughput than previous microfluidic designs. We demonstrate highly efficient trapping and retention of mother cells, determination of the replicative lifespan, and tracking of yeast cells throughout their entire lifespan. Using the high-resolution and large-scale data generated from the high-throughput yeast aging analysis (HYAA) chips, we investigated particular longevity-related changes in cell morphology and characteristics, including critical cell size, terminal morphology, and protein subcellular localization. In addition, because of the significantly improved retention rate of yeast mother cell, the HYAA-Chip was capable of demonstrating replicative lifespan extension by calorie restriction.microfluidics | high-throughput | replicative aging | calorie restriction | Saccharomyces cerevisiae

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“…Trisomic human (Segal and McCoy 1974;Stingele et al 2012) and mouse (Williams et al 2008) cells exhibit decreased proliferation, and cells harboring mutations that promote chromosomal instability (CIN) proliferate either normally (Babu et al 2003;Jeganathan et al 2007;Weaver et al 2007) or more slowly, indicating that aneuploidy is, at best, fitness-neutral. Furthermore, studies in mouse models of CIN and Down syndrome (DS) have demonstrated that these conditions can both promote and inhibit tumorigenesis in vivo (Pfau and Amon 2012). These observations make clear the need for additional experimental systems to assess the effects of aneuploidy per se on cell proliferation in vivo.…”

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confidence: 99%

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

et al. 2016

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Aneuploidy, an imbalanced karyotype, is a widely observed feature of cancer cells that has long been hypothesized to promote tumorigenesis. Here we evaluate the fitness of cells with constitutional trisomy or chromosomal instability (CIN) in vivo using hematopoietic reconstitution experiments. We did not observe cancer but instead found that aneuploid hematopoietic stem cells (HSCs) exhibit decreased fitness. This reduced fitness is due at least in part to the decreased proliferative potential of aneuploid hematopoietic cells. Analyses of mice with CIN caused by a hypomorphic mutation in the gene Bub1b further support the finding that aneuploidy impairs cell proliferation in vivo. Whereas nonregenerating adult tissues are highly aneuploid in these mice, HSCs and other regenerative adult tissues are largely euploid. These findings indicate that, in vivo, mechanisms exist to select against aneuploid cells.

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Chromosomal instability and aneuploidy in cancer: from yeast to man

Cited by 195 publications

References 116 publications

Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation

Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation

High-throughput analysis of yeast replicative aging using a microfluidic system

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

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