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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.)

Early X chromosome inactivation during human preimplantation development revealed by single-cell RNA-sequencing

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Autor(es):
Moreira de Mello, Joana C. ; Fernandes, Gustavo R. ; Vibranovski, Maria D. ; Pereira, Lygia V.
Número total de Autores: 4
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 7, SEP 7 2017.
Citações Web of Science: 19
Resumo

In female mammals, one X chromosome is transcriptionally inactivated (XCI), leading to dosage compensation between sexes, fundamental for embryo viability. A previous study using single-cell RNA-sequencing (scRNA-seq) data proposed that female human preimplantation embryos achieve dosage compensation by downregulating both Xs, a phenomenon named dampening of X expression. Using a novel pipeline on those data, we identified a decrease in the proportion of biallelically expressed X-linked genes during development, consistent with XCI. Moreover, we show that while the expression sum of biallelically expressed X-linked genes decreases with embryonic development, their median expression remains constant, rejecting the hypothesis of X dampening. In addition, analyses of a different dataset of scRNA-seq suggest the appearance of X-linked monoallelic expression by the late blastocyst stage in females, another hallmark of initiation of XCI. Finally, we addressed the issue of dosage compensation between the single active X and autosomes in males and females for the first time during human preimplantation development, showing emergence of X to autosome dosage compensation by the upregulation of the active X chromosome in both male and female embryonic stem cells. Our results show compelling evidence of an early process of X chromosome inactivation during human preimplantation development. (AU)

Processo FAPESP: 15/20844-4 - O papel da gametogênesis na origem e evolução dos genes novos
Beneficiário:Maria Dulcetti Vibranovski
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 09/17481-6 - Estudos da Inativação do Cromossomo X em humanos: iniciação e imprinting
Beneficiário:Joana Carvalho Moreira de Mello
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 15/03610-0 - Análise in silico do estado epigenético do cromossomo X em embriões humanos em estágio pré-implantacional
Beneficiário:Joana Carvalho Moreira de Mello
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
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