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Stem Cell Reports. 2014 May 15;2(6):896-909. doi: 10.1016/j.stemcr.2014.04.003. eCollection 2014.

X Chromosome of female cells shows dynamic changes in status during human somatic cell reprogramming.

Author information

1
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
2
Molecular, Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06511, USA.
3
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.

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.

PMID:
24936474
PMCID:
PMC4050354
DOI:
10.1016/j.stemcr.2014.04.003
[Indexed for MEDLINE]
Free PMC Article
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