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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Aberrant Patterns of X Chromosome Inactivation in a New Line of Human Embryonic Stem Cells Established in Physiological Oxygen Concentrations

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de Oliveira Georges, Juliana Andrea [1, 2] ; Vergani, Naja [1, 2] ; Siqueira Fonseca, Simone Aparecida [1, 2, 3] ; Fraga, Ana Maria [1, 2] ; Moreira de Mello, Joana Carvalho [1, 2] ; Maciel Albuquerque, Maria Cecilia R. [4] ; Fujihara, Litsuko Shimabukuro [4] ; Pereira, Lygia Veiga [1, 2, 3]
Total Authors: 8
[1] Univ Sao Paulo, Mol Genet Lab, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Genet & Evolutionary Biol, Natl Lab Embryon Stem Cell LaNCE, Sao Paulo - Brazil
[3] Sao Paulo Res Fdn FAPESP, Ctr Cell Based Therapy, Sao Paulo - Brazil
[4] Fertivitro Ctr Human Reprod, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: STEM CELL REVIEWS AND REPORTS; v. 10, n. 4, p. 472-479, AUG 2014.
Web of Science Citations: 6

One of the differences between murine and human embryonic stem cells (ESCs) is the epigenetic state of the X chromosomes in female lines. Murine ESCs (mESCs) present two transcriptionally active Xs that will undergo the dosage compensation process of XCI upon differentiation, whereas most human ESCs (hESCs) spontaneously inactivate one X while keeping their pluripotency. Whether this reflects differences in embryonic development of mice and humans, or distinct culture requirements for the two kinds of pluripotent cells is not known. Recently it has been shown that hESCs established in physiological oxygen levels are in a stable pre-XCI state equivalent to that of mESCs, suggesting that culture in low oxygen concentration is enough to preserve that epigenetic state of the X chromosomes. Here we describe the establishment of two new lines of hESCs under physiological oxygen level and the characterization of the XCI state in the 46,XX line BR-5. We show that a fraction of undifferentiated cells present XIST RNA accumulation and single H3K27me foci, characteristic of the inactive X. Moreover, analysis of allele specific gene expression suggests that pluripotent BR-5 cells present completely skewed XCI. Our data indicate that physiological levels of oxygen are not sufficient for the stabilization of the pre-XCI state in hESCs. (AU)

FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
Grantee:Dimas Tadeu Covas
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC