Extensive cellular heterogeneity of X inactivation revealed by single-cell allele-specific expression in human fibroblasts.

Détails

ID Serval
serval:BIB_3DBC9F9CC6B5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Extensive cellular heterogeneity of X inactivation revealed by single-cell allele-specific expression in human fibroblasts.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Garieri M., Stamoulis G., Blanc X., Falconnet E., Ribaux P., Borel C., Santoni F., Antonarakis S.E.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
18/12/2018
Peer-reviewed
Oui
Volume
115
Numéro
51
Pages
13015-13020
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Résumé
X-chromosome inactivation (XCI) provides a dosage compensation mechanism where, in each female cell, one of the two X chromosomes is randomly silenced. However, some genes on the inactive X chromosome and outside the pseudoautosomal regions escape from XCI and are expressed from both alleles (escapees). We investigated XCI at single-cell resolution combining deep single-cell RNA sequencing with whole-genome sequencing to examine allelic-specific expression in 935 primary fibroblast and 48 lymphoblastoid single cells from five female individuals. In this framework we integrated an original method to identify and exclude doublets of cells. In fibroblast cells, we have identified 55 genes as escapees including five undescribed escapee genes. Moreover, we observed that all genes exhibit a variable propensity to escape XCI in each cell and cell type and that each cell displays a distinct expression profile of the escapee genes. A metric, the Inactivation Score-defined as the mean of the allelic expression profiles of the escapees per cell-enables us to discover a heterogeneous and continuous degree of cellular XCI with extremes represented by "inactive" cells, i.e., cells exclusively expressing the escaping genes from the active X chromosome and "escaping" cells expressing the escapees from both alleles. We found that this effect is associated with cell-cycle phases and, independently, with the XIST expression level, which is higher in the quiescent phase (G0). Single-cell allele-specific expression is a powerful tool to identify novel escapees in different tissues and provide evidence of an unexpected cellular heterogeneity of XCI.
Mots-clé
Alleles, Cells, Cultured, Chromosomes, Human, X/genetics, Female, Fibroblasts/cytology, Fibroblasts/metabolism, High-Throughput Nucleotide Sequencing/methods, Humans, Single-Cell Analysis/methods, Transcriptome, X Chromosome Inactivation, X inactivation, XIST, cell cycle, cell heterogeneity, single-cell transcriptomics
Pubmed
Web of science
Création de la notice
13/12/2018 17:17
Dernière modification de la notice
20/08/2019 14:34
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