 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 30, 2013 |
| Title |
Estrogen-Related Receptor γ (ERRγ) Regulates Oxygen-Dependent Expression of Voltage-gated Potassium (K+) Channels and Tissue Kallikrein during Human Trophoblast Differentiation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Estrogen-related receptor γ (ERRγ) serves a critical O2-dependent regulatory role in differentiation of human cytotrophoblasts to syncytiotrophoblast. In this study, we investigated expression of genes encoding tissue kallikreins (KLK1) and voltage-gated K+ channels (KV7) during differentiation of human trophoblasts in culture and the roles of ERRγ and O2 tension in their regulation. Expression of KLK1 and the KV7 channel subunits, KCNQ1, KCNE1, KCNE3, KCNE5, increased during differentiation of cultured human trophoblast cells in a 20% O2 environment. Notably, together with ERRγ, expression of KLK1, KCNQ1, KCNE1, KCNE3 and KCNE5 was markedly reduced when cells were cultured in a hypoxic environment (2% O2). Moreover, upon transduction of trophoblast cells with shRNAs for endogenous ERRγ, KLK1, KCNQ1, KCNE1 and KCNE3 expression was significantly decreased. Promoter and site-directed mutagenesis studies in transfected cells identified putative ERRγ response elements (ERREs) within the KLK1 and KCNE1 5'-flanking regions required for ERRγ -stimulated transcriptional activity. Binding of endogenous ERRγ to these ERREs increased during trophoblast differentiation in culture and was inhibited by hypoxia. The KV7 blocker linopirdine reduced hCG secretion and aggregation of cultured human trophoblasts, suggesting a possible role of KV7 channels in cell fusion and differentiation. Illumina gene expression arrays of cultured human trophoblast cells revealed several genes upregulated during syncytiotrophoblast differentiation and downregulated upon ERRγ knockdown involved in cell differentiation, adhesion, and synthesis of steroid and peptide hormones required for placental development and function. Collectively, these findings suggest that ERRγ mediates O2-dependent expression of genes involved in human trophoblast differentiation, function and vascular homeostasis.
|
| |
|
| Overall design |
Illumina whole genome gene expression array analysis was performed on human trophoblasts before culture, or 72 h after infection with recombinant lentiviruses expressing ERRγ shRNA, or a control, nonsilencing shRNA. RNA from three independent experiments using placental tissues from three abortuses was extracted by miRNeasy® Mini Kit (Qiagen, Maryland, USA). RNA was labeled and hybridized to an Illumina HumanHT-12 v4 BeadChip, according to the manufacturer’s protocol.
|
| |
|
| Contributor(s) |
Luo Y, Kumar P, Mendelson CR |
| Citation(s) |
23584901 |
| Submission date |
Apr 29, 2013 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Scott Andrew Ochsner |
| E-mail(s) |
sochsner@bcm.edu
|
| Phone |
713-798-6227
|
| Organization name |
Baylor College of Medicine
|
| Department |
Molecular and Cellular Biology
|
| Lab |
SPP: Signaling Pathways Project
|
| Street address |
One Baylor Plaza
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (9)
|
|
| Relations |
| BioProject |
PRJNA200577 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46463_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE46463_non-normalized.txt.gz |
2.7 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...