Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures

Tomokazu Amano, Emiko Jeffries, Misa Amano, Akihiro C. Ko, Hong Yu, Minoru Ko

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)331-342
Number of pages12
JournalDNA Research
Volume22
Issue number5
DOIs
Publication statusPublished - 2015 May 6

Fingerprint

Aneuploidy
Down Syndrome
Cell Culture Techniques
Chromosomes, Human, Pair 21
Biological Products
Fibroblasts
Chromosomes, Human, 21-22 and Y
Exome
Sendai virus
Polyploidy
Blastocyst
Trisomy 18
Fluorescence In Situ Hybridization
Karyotype
Cultured Cells
Stem Cells
Cell Count
Chromosomes
Messenger RNA
Genes

Keywords

  • aneuploidy
  • Down syndrome
  • Edwards syndrome
  • human fibroblast cells
  • ZSCAN4

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology

Cite this

Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures. / Amano, Tomokazu; Jeffries, Emiko; Amano, Misa; Ko, Akihiro C.; Yu, Hong; Ko, Minoru.

In: DNA Research, Vol. 22, No. 5, 06.05.2015, p. 331-342.

Research output: Contribution to journalArticle

Amano, Tomokazu ; Jeffries, Emiko ; Amano, Misa ; Ko, Akihiro C. ; Yu, Hong ; Ko, Minoru. / Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures. In: DNA Research. 2015 ; Vol. 22, No. 5. pp. 331-342.
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