Autonomous trisomic rescue of Down syndrome cells

Down syndrome is the most frequent chromosomal abnormality among live-born infants. All Down syndrome patients have mental retardation and are prone to develop early onset Alzheimer's disease. However, it has not yet been elucidated whether there is a correlation between the phenotype of Down s...

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Bibliographic Details
Published in:Laboratory investigation 2019-06, Vol.99 (6), p.885-897
Main Authors: Inoue, Momoko, Kajiwara, Kazuhiro, Yamaguchi, Ayumi, Kiyono, Tohru, Samura, Osamu, Akutsu, Hidenori, Sago, Haruhiko, Okamoto, Aikou, Umezawa, Akihiro
Format: Article
Language:English
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Cells, Cultured
Chemical treatment
Chromosome 21
Chromosome aberrations
Chromosomes
Cultivation
Diploids
Down syndrome
Down Syndrome - genetics
Down's syndrome
Drug screening
Female
Humans
Induced Pluripotent Stem Cells
Infants
Irradiation
Laboratory Medicine
Medicine
Medicine & Public Health
Mosaicism
Organic chemistry
Pathology
Phenotypes
Pluripotency
Pregnancy
Prenatal diagnosis
Radiation
Stem cells
Trisomy
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Summary:Down syndrome is the most frequent chromosomal abnormality among live-born infants. All Down syndrome patients have mental retardation and are prone to develop early onset Alzheimer's disease. However, it has not yet been elucidated whether there is a correlation between the phenotype of Down syndrome and the extra chromosome 21. In this study, we continuously cultivated induced pluripotent stem cells (iPSCs) with chromosome 21 trisomy for more than 70 weeks, and serendipitously obtained revertant cells with normal chromosome 21 diploids from the trisomic cells during long-term cultivation. Repeated experiments revealed that this trisomy rescue was not due to mosaicism of chromosome 21 diploid cells and occurred at an extremely high frequency. We herewith report the spontaneous correction from chromosome 21 trisomy to disomy without genetic manipulation, chemical treatment or exposure to irradiation. The revertant diploid cells will possibly serve a reference for drug screening and a raw material of regenerative medicinal products for cell-based therapy.
ISSN:0023-6837
1530-0307
DOI:10.1038/s41374-019-0230-0