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          Institute: MPI für molekulare Biomedizin     Collection: Yearbook 2013     Display Documents

ID: 648326.0, MPI für molekulare Biomedizin / Yearbook 2013
Reestablishment of the inactive X chromosome to the ground state through cell fusion-induced reprogramming
Authors:Choi, H. W.; Kim, J. S.; Jang, H. J.; Choi, S.; Kim, J. H.; Scholer, H. R.; Do, J. T.
Date of Publication (YYYY-MM-DD):2012-12
Title of Journal:Cellular and Molecular Life Sciences
Issue / Number:23
Start Page:4067
End Page:4077
Review Status:Internal review
Audience:Not Specified
Abstract / Description:The restricted gene expression pattern of a differentiated cell can be reversed by fusion of the somatic cell with a more developmentally potent cell type, such as an embryonic stem (ES) cell. During this reprogramming process, somatic cells obtain most of the characteristics of pluripotent cells. Reactivation of an inactive X chromosome (Xi) is an important epigenetic marker confirming the pluripotent reprogramming of somatic cells. Female somatic cells contain one active X chromosome (Xa) and one Xi, and following the fusion of these cells with male ES cells, the Xi becomes activated, resulting in XaXaXaY fusion hybrid cells. To monitor Xi reactivation, transgenic female neural stem cells (fNSCs) carrying a green fluorescent protein (GFP) reporter gene expressed on the Xa (X-GFP), but not on the Xi, were used for reprogramming. XaXi(GFP) NSCs, whose GFP reporter was silenced, were fused with HM1 ES cells (XY) to induce pluripotent reprogramming. The Xi(GFP) of NSCs were found to be activated on day 4 post-fusion, indicating reactivation of the Xi. Hybrid cells showed pluripotent cell-specific characteristics cells including inactivation of the NSC marker Nestin, DNA demethylation of Oct4, DNA methylation of Nestin, and reactivation of the Xi. Following differentiation of the (GFP-positive) hybrid cells through embryoid body formation, the proportion of GFP-negative cells was found to be approximately 26 %, indicating that there was random inactivation of one of the three Xas. Here, we showed that the Xi of somatic cells is reprogrammed to the Xa state and that cellular differentiation occurs randomly, i.e., regardless of the Xa or Xi state, indicating that the memory of the Xi of somatic cells has been erased and reset to the ground state (i.e., inner cell mass-like state), indicating that random X-chromosome inactivation occurs upon differentiation.
Free Keywords:reprogramming; stem cells; cell fusion; x-chromosome inactivation; pluripotency; embryonic stem-cells; somatic-cells; pluripotent cells; xist expression; cloned embryos; germ-cells; memory; mice
External Publication Status:published
Document Type:Article
Communicated by:keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Konkuk Univ, Dept Anim Biotechnol, Coll Anim Biosci & Technol, Seoul 143701, South Korea Konkuk Univ, Dept Anim Biotechnol, Coll Anim Biosci & Technol, Seoul 143701, South Korea Konkuk Univ, Dept Anim Biotechnol, Coll Anim Biosci & Technol, Seoul 143701, South Korea CHA Univ, Dept Biomed Sci, Seoul 135081, South Korea Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, Germany CHA Univ, Dept Biomed Sci, Pochan Si, Gyeonggi Do, South Korea %G English
Identifiers:ISSN:1420-682X %R Doi 10.1007/S00018-012-1139-6 [ID No:1]
ISI:000310868200016 [ID No:2]
ISI:000310868200016 [ID No:3]
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