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| Status |
Public on Mar 29, 2022 |
| Title |
Hypoxia-inducible factor 1 signaling drives placental aging and can elicit inflammatory changes in uterine myocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Placental aging has been proposed to promote labor onset, but specific mechanisms remain elusive. An unbiased transcriptomic analysis of healthy mouse placenta revealed that hypoxia-inducible factor 1 (HIF-1) stabilization is a hallmark of advanced gestational timepoints, accompanied by mitochondrial dysfunction and cellular senescence. We validated these gestational age-associated changes through similar findings in human placenta. In parallel in primary mouse trophoblasts and human choriocarcinoma JAR cells, we modeled HIF-1 induction using prolyl hydroxylase inhibitors cobalt chloride (CoCl2) and dimethyloxalylglycine (DMOG), and demonstrated that mitochondrial dysfunction and cellular senescence occur secondary to HIF-1 stabilization. Whole transcriptome analysis revealed that HIF-1 stabilization in JAR cells recapitulated the dysregulation of several pathways observed in aged placenta. Further, conditioned media from cultured trophoblasts following HIF-1 induction is sufficient to induce a contractile phenotype in immortalized uterine myocytes, suggesting a mechanism by which the aging placenta may help drive the transition from uterine quiescence to contractility at the onset of labor.
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| Overall design |
RNA was isolated from JAR choriocarcinoma cells following six days of culture with 100µM CoCl2 versus control conditions (six replicates each) for expression profiling by high-throughput sequencing
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| Contributor(s) |
Parikh S, Ciampa E |
| Citation(s) |
37610425 |
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| Submission date |
Mar 23, 2022 |
| Last update date |
Sep 14, 2023 |
| Contact name |
Erin Ciampa |
| E-mail(s) |
eciampa@bidmc.harvard.edu
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| Phone |
617-667-5811
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| Organization name |
Beth Israel Deaconess Medical Center
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| Street address |
99 Brookline Avenue, RN-345
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (10)
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| GSM5968637 |
JAR cells, untreated, 6-day timepoint, mRNA, rep 2 |
| GSM5968638 |
JAR cells, untreated, 6-day timepoint, mRNA, rep 4 |
| GSM5968639 |
JAR cells, untreated, 6-day timepoint, mRNA, rep 5 |
| GSM5968640 |
JAR cells, untreated, 6-day timepoint, mRNA, rep 6 |
| GSM5968641 |
JAR cells, untreated, 6-day timepoint, mRNA, rep 8 |
| GSM5968642 |
JAR cells, treated with 100µm-CoCl2, 6-day timepoint, mRNA, rep 2 |
| GSM5968643 |
JAR cells, treated with 100µm-CoCl2, 6-day timepoint, mRNA, rep 4 |
| GSM5968644 |
JAR cells, treated with 100µm-CoCl2, 6-day timepoint, mRNA, rep 5 |
| GSM5968645 |
JAR cells, treated with 100µm-CoCl2, 6-day timepoint, mRNA, rep 7 |
| GSM5968646 |
JAR cells, treated with 100µm-CoCl2, 6-day timepoint, mRNA, rep 12 |
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| Relations |
| BioProject |
PRJNA819113 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE199278_RAW.tar |
28.0 Mb |
(http)(custom) |
TAR (of TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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