Enhanced apoptosis during early neuronal differentiation in mouse ES cells with autosomal imbalance

Kai, Yoshiteru; Wang, Chi Chiu; Kishigami, Satoshi; Kazuki, Yasuhiro; Abe, Satoshi; Takiguchi, Masato; Shirayoshi, Yasuaki; Inoue, Toshiaki; Ito, Hisao; Wakayama, Teruhiko; Oshimura, Mitsuo

doi:10.1038/cr.2008.305

Cited by 14 publications

(13 citation statements)

References 36 publications

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“…T21-ESCs produce defective neural stem cells (NSCs) that exhibit high levels of apoptosis 123 . This result reproduces in an isogenic human induced pluripotent stem cell (hiPSC) model comparing hiPSC lines that are genetically identical and that differ only in having three or two HSA21 (D.N., unpublished observations), as well as embryoid bodies (the first in vitro structure obtained when ESCs stop being cultured in pluripotent condition and are allowed to differentiate) with a significant reduction of the neuroectodermal progenitor compartment, suggesting aberrant DS-ESC differentiation 100 .…”

Section: Stem Cell Availability and Fitnessmentioning

confidence: 99%

Tumorigenesis in Down's syndrome: big lessons from a small chromosome

2012

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If assessed by a number of criteria for cancer predisposition, Down's syndrome (DS) should be an overwhelmingly cancer-prone condition. Although childhood leukaemias occur more frequently in DS, paradoxically, individuals with DS have a markedly lower incidence of most solid tumours. Understanding the mechanisms that are capable of overcoming such odds could potentially open new routes for cancer prevention and therapy. In this Opinion article, we discuss recent reports that suggest unique and only partially understood mechanisms behind this paradox, including tumour repression, anti-angiogenic effects and stem cell ageing and availability.

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Section: Stem Cell Availability and Fitnessmentioning

confidence: 99%

Tumorigenesis in Down's syndrome: big lessons from a small chromosome

2012

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“…Moreover, recent research provides evidence that oxidative stress is elevated in the Ts1Cje mouse, suggesting that one or more genes trisomic in this model, likely contribute to DS-associated oxidative stress[61]. Interestingly, aneuploidy of chromosomes other than Hsa21 also results in elevated apoptosis and reduced cellular proliferation[62],[63].…”

Section: Recent Breakthroughs In Our Understanding Of Phenotypes Arismentioning

confidence: 86%

Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21

Ruparelia

Wiseman

Sheppard

et al. 2010

Journal of Biomedical Research

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Chromosome copy number aberrations, anueploidies, are common in the human population but generally lethal. However, trisomy of human chromosome 21 is compatible with life and people born with this form of aneuploidy manifest the features of Down syndrome, named after Langdon Down who was a 19th century British physician who first described a group of people with this disorder. Down syndrome includes learning and memory deficits in all cases, as well as many other features which vary in penetrance and expressivity in different people. While Down syndrome clearly has a genetic cause - the extra dose of genes on chromosome 21 - we do not know which genes are important for which aspects of the syndrome, which biochemical pathways are disrupted, or, generally how design therapies to ameliorate the effects of these disruptions. Recently, with new insights gained from studying mouse models of Down syndrome, specific genes and pathways are being shown to be involved in the pathogenesis of the disorder. This is opening the way for exciting new studies of potential therapeutics for aspects of Down syndrome, particularly the learning and memory deficits.

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“…These cells have been used to generate chimeric mice to model Down syndrome, showing a high correlation between retention of chromosome 21 in tissues such as brain, heart and thymus, and alteration in the phenotype [18,104]. In more recent studies, in vitro and in vivo differentiation of transchro mosomal mESCs revealed compromised neuro nal cell populations not only in trisomy 21, but also in other human trisomies [105][106][107][108]. Human embryonic stem cells represent an alternative and more accurate system for mod eling human whole chromosome aneuploidies.…”

Section: Future Science Groupmentioning

confidence: 99%

Aneuploid Human Embryonic Stem Cells: Origins and Potential for Modeling Chromosomal Disorders

Biancotti¹,

Benvenisty

2011

Regen. Med.

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Chromosomal aneuploidies are widely recognized genetic disorders in humans that often lead to spontaneous abortion. Aneuploid fetuses that survive to term commonly exhibit impaired developmental growth and mental retardation in addition to multiple congenital malformations. Preimplantation genetic screening is used to detect chromosomal aneuploidies in early embryos. Human embryonic stem cell (ESC) cell lines generated from aneuploid embryos created a unique repository of cell lines. The spectrum of aneuploidies in these ESC lines reflects the range of common embryonic chromosomal aberrations and significantly differs from the spectrum of aneuploid human ESC lines generated by cell adaptation in culture. The aneuploid human ESC lines represent an excellent model to study human chromosomal abnormalities especially in the early stages of development.

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Enhanced apoptosis during early neuronal differentiation in mouse ES cells with autosomal imbalance

Cited by 14 publications

References 36 publications

Tumorigenesis in Down's syndrome: big lessons from a small chromosome

Tumorigenesis in Down's syndrome: big lessons from a small chromosome

Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21

Aneuploid Human Embryonic Stem Cells: Origins and Potential for Modeling Chromosomal Disorders

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