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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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]
Número total de Autores: 8
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: STEM CELL REVIEWS AND REPORTS; v. 10, n. 4, p. 472-479, AUG 2014.
Citações Web of Science: 6
Resumo

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)

Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
Beneficiário:Dimas Tadeu Covas
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs