Open AccessInduced pluripotent stem cell generation from a man carrying a complex chromosomal rearrangement as a genetic model for infertility studies
Author(s) -
Aurélie Mouka,
V. Izard,
Gérard Tachdjian,
Sophie Brisset,
F Yates,
Anne Mayeur,
Loïc Drévillon,
Rafika Jarray,
Philippe Leboulch,
Leïla MaoucheChrétien,
Lucie Tosca
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep39760
Subject(s) - biology , induced pluripotent stem cell , chromosomal rearrangement , genetics , karyotype , germ cell , fluorescence in situ hybridization , microbiology and biotechnology , chromosome , embryonic stem cell , gene
Despite progress in human reproductive biology, the cause of male infertility often remains unknown, due to the lack of appropriate and convenient in vitro models of meiosis. Induced pluripotent stem cells (iPSCs) derived from the cells of infertile patients could provide a gold standard model for generating primordial germ cells and studying their development and the process of spermatogenesis. We report the characterization of a complex chromosomal rearrangement (CCR) in an azoospermic patient, and the successful generation of specific-iPSCs from PBMC-derived erythroblasts. The CCR was characterized by karyotype, fluorescence in situ hybridization and oligonucleotide-based array-comparative genomic hybridization. The CCR included five breakpoints and was caused by the inverted insertion of a chromosome 12 segment into the short arm of one chromosome 7 and a pericentric inversion of the structurally rearranged chromosome 12. Gene mapping of the breakpoints led to the identification of a candidate gene, SYCP3 . Erythroblasts from the patient were reprogrammed with Sendai virus vectors to generate iPSCs. We assessed iPSC pluripotency by RT-PCR, immunofluorescence staining and teratoma induction. The generation of specific-iPSCs from patients with a CCR provides a valuable in vitro genetic model for studying the mechanisms by which chromosomal abnormalities alter meiosis and germ cell development.