Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures
Autor: | Tomokazu Amano, Misa Amano, Akihiro C. Ko, Minoru S.H. Ko, Emiko Jeffries, Hong Yu |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Down syndrome
Genetic Vectors Primary Cell Culture Aneuploidy Trisomy Biology human fibroblast cells Sendai virus Mice Genetics medicine Animals Humans ZSCAN4 RNA Messenger Molecular Biology Cells Cultured In Situ Hybridization Fluorescence Edwards syndrome Karyotype Mouse Embryonic Stem Cells General Medicine Genetic Therapy Full Papers medicine.disease Embryonic stem cell Molecular biology DNA-Binding Proteins Ploidy Stem cell Chromosome 21 Chromosomes Human Pair 18 Trisomy 18 Syndrome Transcription Factors |
Zdroj: | DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes |
ISSN: | 1756-1663 1340-2838 |
Popis: | Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome—the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4. |
Databáze: | OpenAIRE |
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