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| Status |
Public on Oct 19, 2020 |
| Title |
Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation [Male] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
X chromosome dosage compensation is one of the most important epigenetic events in female mammalian development. Although the mouse has served as the primary model to study how genetic equality is established between male and female mammals, it is now appreciated that these mechanisms are not fully conserved in humans. Using human primordial germ cells (hPGCs) as a model together with single cell RNA-sequencing, in vitro differentiation of hPGC like cells and human embryo attachment culture, we show that X-linked gene expression in female hPGCs is compensated to levels found in female somatic cells though a mechanism related to X chromosome dampening rather than X chromosome inactivation. Loss of dampening and decompensation of both X chromosomes occurs when female hPGCs enter meiosis and is coincident with loss of the long non-coding RNAs XIST and XACT. In contrast, differentiation of male hPGCs results in no change in compensation despite loss of XACT. Taken together, future studies of X-linked gene regulation and function in human germ cell development and fertility must take into account the unique and sexually dimorphic dosage compensation occurring during in the prenatal human germline prior to birth.
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| Overall design |
In our work, we performed single cell RNA-sequencing (scRNA-seq) with 10x Genomics on 6 different male human prenatal testes from 6 different developmental timepoints: Week 6, 7, 8, 12, 15 and 16 post fertilization. In total, we sequenced ~30,000 gonadal somatic and germ cells to uncover X chromosome dynamics during female and male germline development.
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| Contributor(s) |
Chitiashvili T, Plath K, Clark A |
| Citation(s) |
33257808 |
| Submission date |
Jan 09, 2020 |
| Last update date |
Feb 11, 2021 |
| Contact name |
Tsotne Chitiashvili |
| E-mail(s) |
tsotne@ucla.edu
|
| Organization name |
University of California - Los Angeles
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| Street address |
615 Charles E Young Dr S
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE143381 |
Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation [Female] |
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| Relations |
| BioProject |
PRJNA600212 |
| SRA |
SRP240899 |
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