title: X Chromosome of female cells shows dynamic changes in status during human somatic cell reprogramming.
abstract: Induced pluripotent stem cells (iPSCs) acquire embryonic stem cell (ESC)-like epigenetic states, including the X chromosome. Previous studies reported that human iPSCs retain the inactive X chromosome of parental cells, or acquire two active X chromosomes through reprogramming. Most studies investigated the X chromosome states in established human iPSC clones after completion of reprogramming. Thus, it is still not fully understood when and how the X chromosome reactivation occurs during reprogramming. Here, we report a dynamic change in the X chromosome state throughout reprogramming, with an initial robust reactivation of the inactive X chromosome followed by an inactivation upon generation of nascent iPSC clones. iPSCs with two active X chromosomes or an eroded X chromosome arise in passaging iPSCs. These data provide important insights into the plasticity of the X chromosome of human female iPSCs and will be crucial for the future application of such cells in cell therapy and X-linked disease modeling.
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Kun-Yong
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Eriona
authors.initials: E
authors.lastname: Hysolli
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Molecular, Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06511, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA ; Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul 135-080, Republic of Korea.
authors.forename: Yong-Wook
authors.initials: YW
authors.lastname: Jung
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Sherman Morton
authors.initials: SM
authors.lastname: Weissman
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
mesh_terms: D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics