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| Status |
Public on Oct 04, 2022 |
| Title |
Monosomy X in isogenic human iPSC-derived trophoblast model impacts expression modules preserved in human placenta [CytoSNP-850k] |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
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| Summary |
Mammalian sex chromosomes encode homologous X/Y gene pairs that were retained on the male Y and escape X chromosome inactivation (XCI) in females. Inferred to reflect X/Y-pair dosage sensitivity, monosomy X is a leading cause of miscarriage in humans with near full penetrance. This phenotype is shared with many other mammals but not the mouse, which offers sophisticated genetic tools to generate sex chromosomal aneuploidy but also tolerates its developmental impact. To address this critical gap, we generated X-monosomic human induced pluripotent stem cells (hiPSCs) alongside otherwise isogenic euploid controls from male and female mosaic samples. Phased genomic variants of these hiPSC panels enable systematic investigation of X/Y dosage-sensitive features using in vitro models of human development. Here, we demonstrate the utility of these validated hiPSC lines to test how X/Y-linked gene dosage impacts a widely-used model for the human syncytiotrophoblast. While these isogenic panels trigger a GATA2/3 and TFAP2A/C -driven trophoblast gene circuit irrespective of karyotype, differential expression implicates monosomy X in altered levels of placental genes, and in secretion of placental growth factor (PlGF) and human chorionic gonadotropin (hCG). Remarkably, weighted gene co-expression network modules that significantly reflect these changes are also preserved in first-trimester chorionic villi and term placenta. Our results suggest monosomy X may skew trophoblast cell type composition and function, and that the compound haploinsufficiency of the pseudoautosomal region likely plays a key role in these changes.
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| Overall design |
Genomic DNA was isolated from the hiPSCs and analyzed by CytoSNP-850k Infinium bead array (Illumina)
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| Contributor(s) |
Ahern DT, Bansal P, Armillei MK, Faustino I, Kondaveeti Y, Glatt-Deeley HR, Banda EC, Pinter SF |
| Citation(s) |
36161909 |
| Submission date |
Jun 28, 2022 |
| Last update date |
Oct 05, 2022 |
| Contact name |
Stefan F Pinter |
| E-mail(s) |
spinter@uchc.edu
|
| Organization name |
University of Connecticut, UConn Health
|
| Department |
Genetics and Genome Sciences
|
| Lab |
Pinter lab
|
| Street address |
263 Farmington Avenue
|
| City |
Farmington |
| State/province |
CT |
| ZIP/Postal code |
06030-6403 |
| Country |
USA |
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| Platforms (1) |
| GPL19718 |
IIllumina Infinium human CytoSNP-850K BeadChip |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE207114 |
Monosomy X in isogenic human iPSC-derived trophoblast model impacts expression modules preserved in human placenta |
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| Relations |
| BioProject |
PRJNA853754 |
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