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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.)

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

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Author(s):
Moreira de Mello, Joana C. ; Fernandes, Gustavo R. ; Vibranovski, Maria D. ; Pereira, Lygia V.
Total Authors: 4
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, SEP 7 2017.
Web of Science Citations: 17
Abstract

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)

FAPESP's process: 15/20844-4 - The role of gametogenesis on the origin and evolution of new genes
Grantee:Maria Dulcetti Vibranovski
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 09/17481-6 - X-chromosome inactivation in humans: initiation and imprinting
Grantee:Joana Carvalho Moreira de Mello
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/03610-0 - In silico analysis of the X-chromosome epigenetic state in human pre-implantation embryos
Grantee:Joana Carvalho Moreira de Mello
Support type: Scholarships in Brazil - Post-Doctorate
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