Stable X chromosome reactivation in female human induced pluripotent stem cells.
Stem Cell Reports
; 4(2): 199-208, 2015 Feb 10.
Article
em En
| MEDLINE
| ID: mdl-25640760
ABSTRACT
In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI) in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female human fibroblasts into induced pluripotent stem cells (iPSCs) leads to reactivation of the inactive X chromosome (Xi), we have generated iPSC lines from fibroblasts heterozygous for large X-chromosomal deletions. These fibroblasts show completely skewed XCI of the mutated X chromosome, enabling monitoring of X chromosome reactivation (XCR) and XCI using allele-specific single-cell expression analysis. This approach revealed that XCR is robust under standard culture conditions, but does not prevent reinitiation of XCI, resulting in a mixed population of cells with either two active X chromosomes (Xas) or one Xa and one Xi. This mixed population of XaXa and XaXi cells is stabilized in naive human stem cell medium, allowing expansion of clones with two Xas.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Transcricional
/
Cromossomos Humanos X
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Células-Tronco Pluripotentes Induzidas
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article