title: Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies.
abstract: Turner syndrome is caused by complete or partial loss of the second sex chromosome and is characterized by spontaneous fetal loss in >90% of conceptions. Survivors possess an array of somatic and germline clinical characteristics. Induced pluripotent stem cells (iPSCs) offer an opportunity for insight into genetic requirements of the X chromosome linked to Turner syndrome. We derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We demonstrate that two X chromosomes are not necessary for reprogramming or maintenance of pluripotency and that there are minimal differences in gene expression, at the single cell level, linked to X chromosome aneuploidies. Formation of germ cells, as assessed in vivo through a murine xenotransplantation model, indicated that undifferentiated iPSCs, independent of X chromosome composition, are capable of forming germ-cell-like cells (GCLCs) in vivo. In combination with clinical data regarding infertility in women with X chromosome aneuploidies, results suggest that two intact X chromosomes are not required for human germ cell formation, qualitatively or quantitatively, but rather are likely to be required for maintenance of human germ cells to adulthood.
authors.affiliation: 1] Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA [2].
authors.forename: Antonia A
authors.initials: AA
authors.lastname: Dominguez
authors.affiliation: Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.
authors.forename: H Rosaria
authors.initials: HR
authors.lastname: Chiang
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Sukhwani
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kyle E
authors.initials: KE
authors.lastname: Orwig
authors.affiliation: 1] Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA [2].
authors.forename: Renee A
authors.initials: RA
authors.lastname: Reijo Pera
mesh_terms: D000782:Aneuploidy; D000818:Animals; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005854:Germ Cells / Q000254:growth & development / Q000473:pathology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology*; D051379:Mice; D059010:Single-Cell Analysis; D014183:Transplantation, Heterologous; D014424:Turner Syndrome / Q000235:genetics* / Q000473:pathology