 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 12, 2017 |
| Title |
Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts [AB81] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD development and progression. In our study, genome-wide expression profiles of more than 200 renal biopsies from patients with different CKD stages revealed significant correlation of HIF-target genes with eGFR in glomeruli and tubulointerstitium. These correlations were positive and negative and in part compartment-specific. Microarrays of proximal tubular cells and podocytes with stable HIF1α and/or HIF2α suppression displayed cell type-specific HIF1/HIF2-dependencies as well as dysregulation of several pathways. WGCNA analysis identified gene sets that were highly coregulated within modules. Characterization of the modules revealed common as well as cell group- and condition-specific pathways, GO-Terms and transcription factors. Gene expression analysis of the hypoxia-interconnected pathways in patients with different CKD stages revealed an increased dysregulation with loss of renal function. In conclusion, our data clearly point to a compartment- and cell type-specific dysregulation of hypoxia-associated gene transcripts and might help to improve the understanding of hypoxia, HIF dysregulation, and transcriptional program response in CKD.
|
| |
|
| Overall design |
Immortalized human podocytes (AB81) and human proximal tubular epithelial cells (HK2) with stable HIF1 and/or HIF2 suppression were subjected to normoxia (N, 20 % O2) or hypoxia (H, 1% O2) for 24h and gene expression profiles were generated. 3 replicates per group.
|
| |
|
| Contributor(s) |
Shved N, Warsow G, Eichinger FH, Hoogewijs D, Brandt S, Wild P, Kretzler M, Cohen CD, Lindenmeyer MT |
| Citation(s) |
28819298 |
| |
| Submission date |
May 25, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Felix Eichinger |
| E-mail(s) |
eichinge@umich.edu
|
| Organization name |
The University of Michigan
|
| Department |
Division of Nephrology
|
| Street address |
1150 W. Medical Center Drive
|
| City |
Ann Arbor |
| State/province |
Michigan |
| ZIP/Postal code |
48109 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19109 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array [CDF: Brainarray HGU133Plus2_Hs_ENTREZG_v18] |
|
| Samples (24)
|
| GSM2641105 |
AB81 hypoxia, HIF1kd, a |
| GSM2641106 |
AB81 hypoxia, HIF1kd, b |
| GSM2641107 |
AB81 hypoxia, HIF1kd, c |
| GSM2641108 |
AB81, hypoxia, HIF2kd, a |
| GSM2641109 |
AB81, hypoxia, HIF2kd, b |
| GSM2641110 |
AB81, hypoxia, HIF2kd, c |
| GSM2641111 |
AB81, hypoxia, HIF12kd, a |
| GSM2641112 |
AB81, hypoxia, HIF12kd, b |
| GSM2641113 |
AB81, hypoxia, HIF12kd, c |
| GSM2641114 |
AB81, normoxia, wild type, a |
| GSM2641115 |
AB81, normoxia, wild type, b |
| GSM2641116 |
AB81, normoxia, wild type, c |
| GSM2641117 |
AB81, normoxia, HIF1kd, a |
| GSM2641118 |
AB81, normoxia, HIF1kd, b |
| GSM2641119 |
AB81, normoxia, HIF1kd, c |
| GSM2641120 |
AB81, normoxia, HIF2kd, a |
| GSM2641121 |
AB81, normoxia, HIF2kd, b |
| GSM2641122 |
AB81, normoxia, HIF2kd, c |
| GSM2641123 |
AB81, normoxia, HIF12kd, a |
| GSM2641124 |
AB81, normoxia, HIF12kd, b |
| GSM2641125 |
AB81, normoxia, HIF12kd, c |
|
| This SubSeries is part of SuperSeries: |
| GSE99340 |
Transcriptome-based network analysis reveals renal cell type-specific dysregulation of hypoxia-associated transcripts |
|
| Relations |
| BioProject |
PRJNA388160 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99323_RAW.tar |
125.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...