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| Status |
Public on Apr 17, 2021 |
| Title |
Ischemia Reperfusion of Lung Transplant Setting Differentially Regulates Transcriptomic Profiles between Human Lung Endothelial and Epithelial Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Our understanding on mechanisms of ischemia-reperfusion induced lung injury during lung preservation and transplantation is based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic time (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with serum containing culture medium to similar lung transplantation. Cell morphology, viability and transcriptomic profiles were studied. Ischemia-reperfusion induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effects on these phenotypic characteristics. After CIT 18 h, protein biosynthesis related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene cluster in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell type dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
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| Overall design |
This study compared gene expression of BEAS2B cells and HPMEC cells cultured in vitro. 5 conditions were simulated for each cell type: untreated (growth media), 6 hours cold ischemia, 18 hours cold ischemia, 6 hours cold ischemia + 2 hours reperfusion, 18 hours cold ischemia + 2 hours reperfusion
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| Contributor(s) |
Saren G, Wong A, Lu Y, Baciu C, Zhou W, Zamel R, Soltanieh S, Sugihara J, Liu M |
| Citation(s) |
34685693 |
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| Submission date |
Apr 16, 2021 |
| Last update date |
Oct 25, 2021 |
| Contact name |
Aaron Wong |
| E-mail(s) |
wongakk7@gmail.com
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| Organization name |
University Health Network
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| Department |
TGHRI
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| Lab |
Aaron Wong
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| Street address |
101 College Street
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 1L7 |
| Country |
Canada |
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| Platforms (1) |
| GPL20103 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [CDF: hugene20st_Hs_ENTREZG.cdf, Brainarray version 19.0.0] |
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| Samples (39)
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| Relations |
| BioProject |
PRJNA722486 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE172222_RAW.tar |
345.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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