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Generation of a novel isogenic trisomy panel in human embryonic stem cells via microcell-mediated chromosome transfer

Author:
Hiramatsu, Kei, Abe, Satoshi, Kazuki, Kanako, Osaki, Mitsuhiko, Kajitani, Naoyo, Yakura, Yuwna, Oshimura, Mitsuo, Kazuki, Yasuhiro
Source:
Biochemical and biophysical research communications 2019 v.508 no.2 pp. 603-607
ISSN:
0006-291X
Subject:
Down syndrome, carcinogenesis, cell lines, chromosomes, death, embryonic germ layers, embryonic stem cells, epigenetics, gene overexpression, genes, genetic background, humans, models, neurogenesis, patients, phenotype, trisomics
Abstract:
Aneuploidy is the gain or loss of a chromosome. Down syndrome or trisomy (Ts) 21 is the most frequent live-born aneuploidy syndrome in humans and extensively studied using model mice. However, there is no available model mouse for other congenital Ts syndromes, possibly because of the lethality of Ts in vivo, resulting in the lack of studies to identify the responsible gene(s) for aneuploid syndromes. Although induced pluripotent stem cells derived from patients are useful to analyse aneuploidy syndromes, there are concerns about differences in the genetic background for comparative studies and clonal variations. Therefore, a model cell line panel with the same genetic background has been strongly desired for sophisticated comparative analyses. In this study, we established isogenic human embryonic stem (hES) cells of Ts8, Ts13, and Ts18 in addition to previously established Ts21 by transferring each single chromosome into parental hES cells via microcell-mediated chromosome transfer. Genes on each trisomic chromosome were globally overexpressed in each established cell line, and all Ts cell lines differentiated into all three embryonic germ layers. This cell line panel is expected to be a useful resource to elucidate molecular and epigenetic mechanisms of genetic imbalance and determine how aneuploidy is involved in various abnormal phenotypes including tumourigenesis and impaired neurogenesis.
Agid:
6250480