Single-cell RNA-seq identifies protracted mouse germline X chromosome reactivation dynamics directed by a PRC2-dependent mechanism
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Yaqiong Liu Xianzhong Lau Prabhakaran Munusamy Carlos M Abascal Sherwell Sanchez Daniel Snell Mahesh SangrithiAbstract
Female primordial germ cells (PGCs) undergo X chromosome reactivation (XCR) during genome-wide reprogramming. XCR kinetics and dynamics are poorly understood at a molecular level. Here, we apply single-cell RNA sequencing and chromatin profiling on germ cells from F1 mouse embryos, performing a precise appraisal of XCR spanning from migratory-stage PGCs to gonadal germ cells. Establishment of germ cell sexual dimorphism and X chromosome dosage compensation states in vivo are temporally linked to XCR. Allele-specific analysis evidence that the reactivating X chromosome is minimally active in embryonic day (E)9.5 female PGCs, reactivates gradually, and reaches parity to the active X chromosome in E16.5 oogonia. While Xist is repressed from E10.5 onward, epigenetic memory of X inactivation persists from self-sustained polycomb repressive complex 2 (PRC2) activity. The reactivating X is asymmetrically enriched for histone 3-lysine-27-trimethylation (H3K27me3) at E13.5, which is later reversed, permitting germline gene expression. Our findings relate XCR with PRC2 function in promoting female meiosis.
Journal details
Journal
Developmental Cell
Volume
60
Issue number
9
Pages
1321-1335.e5
Available online
Publication date
Full text links
Publisher website (DOI)
10.1016/j.devcel.2024.12.028
Europe PubMed Central
39798575
Pubmed
39798575
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The publication was previously a preprint.
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