X-Chromosome Dosage Modulates Multiple Molecular and Cellular Properties of Mouse Pluripotent Stem Cells Independently of Global DNA Methylation Levels

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2019 Jan 15

PMID 30639215

Citations 19

Authors

Juan Song

Adrian Janiszewski

Natalie De Geest

Lotte Vanheer

Irene Talon

Mouna El Bakkali

Taeho Oh

Vincent Pasque

Affiliations

Soon will be listed here.

Abstract

Reprogramming female mouse somatic cells into induced pluripotent stem cells (iPSCs) leads to X-chromosome reactivation. The extent to which increased X-chromosome dosage (X-dosage) in female iPSCs compared with male iPSCs leads to differences in the properties of iPSCs is still unclear. We show that chromatin accessibility in mouse iPSCs is modulated by X-dosage. Specific sets of transcriptional regulator motifs are enriched in chromatin with increased accessibility in XX or XY iPSCs. The transcriptome, growth and pluripotency exit are also modulated by X-dosage in iPSCs. To understand how increased X-dosage modulates the properties of mouse pluripotent stem cells, we used heterozygous deletions of the X-linked gene Dusp9. We show that X-dosage regulates the transcriptome, open chromatin landscape, growth, and pluripotency exit largely independently of global DNA methylation. Our results provide insights into how gene dosage modulates the epigenetic and genetic mechanisms that regulate cell identity.

Citing Articles

A PLURIPOTENT STEM CELL PLATFORM FOR IN VITRO SYSTEMS GENETICS STUDIES OF MOUSE DEVELOPMENT.

Glenn R, Do S, Guruvayurappan K, Corrigan E, Santini L, Medina-Cano D bioRxiv. 2024; .

PMID: 38895226 PMC: 11185710. DOI: 10.1101/2024.06.06.597758.

X-chromosome inactivation in human iPSCs provides insight into X-regulated gene expression in autosomes.

Topa H, Benoit-Pilven C, Tukiainen T, Pietilainen O Genome Biol. 2024; 25(1):144.

PMID: 38822397 PMC: 11143737. DOI: 10.1186/s13059-024-03286-8.

Roles of the Rlim-Rex1 axis during X chromosome inactivation in mice.

Wang F, Chander A, Yoon Y, Welton J, Wallingford M, Espejo-Serrano C Proc Natl Acad Sci U S A. 2023; 120(52):e2313200120.

PMID: 38113263 PMC: 10756295. DOI: 10.1073/pnas.2313200120.

Modeling unveils sex differences of signaling networks in mouse embryonic stem cells.

Sultana Z, Dorel M, Klinger B, Sieber A, Dunkel I, Bluthgen N Mol Syst Biol. 2023; 19(11):e11510.

PMID: 37735975 PMC: 10632733. DOI: 10.15252/msb.202211510.

The compleX balancing act of controlling X-chromosome dosage and how it impacts mammalian germline development.

Mattimoe T, Payer B Biochem J. 2023; 480(8):521-537.

PMID: 37096944 PMC: 10212525. DOI: 10.1042/BCJ20220450.

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