title: Human pluripotent stem cells with distinct X inactivation status show molecular and cellular differences controlled by the X-Linked ELK-1 gene.
abstract: Female human pluripotent stem cells show vast heterogeneity regarding the status of X chromosome inactivation. By comparing the gene expression profile of cells with two active X chromosomes (XaXa cells) to that of cells with only one active X chromosome (XaXi cells), a set of autosomal genes was shown to be overexpressed in the XaXa cells. Among these genes, we found significant enrichment for genes regulated by the X-linked transcription factor ELK-1. Comparison of the phenotype of XaXa and XaXi cells demonstrated differences in programmed cell death and differentiation, implying some growth disadvantage of the XaXa cells. Interestingly, ELK-1-overexpressing cells mimicked the phenotype of XaXa cells, whereas knockdown of ELK-1 with small hairpin RNA mimicked the phenotype of XaXi cells. When cultured at low oxygen levels, these cellular differences were considerably weakened. Our analysis implies a role of ELK-1 in the differences between pluripotent stem cells with distinct X chromosome inactivation statuses.
authors.affiliation: Stem Cell Unit, Department of Genetics, Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Bruck
authors.forename: Ofra
authors.initials: O
authors.lastname: Yanuka
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D015536:Down-Regulation; D005260:Female; D023281:Genomics; D006801:Humans; D007150:Immunohistochemistry; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D046228:Microarray Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D059467:Transcriptome; D014162:Transfection; D049951:X Chromosome Inactivation / Q000235:genetics*; D050807:ets-Domain Protein Elk-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C494112:ELK1 protein, human; D050807:ets-Domain Protein Elk-1