Introduction about Kidney Perfusion sc RNAseq Atlas (KPA)
The Pig Kidney Perfusion sc RNAseq Atlas (KPA) database is created to facilitate the application of pigs in xenotransplantation community.
Genetically modified pigs to eliminate human immune rejection of xenografts is one promising solution to the global donor organ shortage.
The development of xenograft transplantation has however been hampered by incomplete understanding of its immune rejection and the inability
to test this in a human transplantation setting. Here we use an ex vivo organ perfusion system with human whole blood to assess the initial
immune activation within the xenograft endothelium and response within immune cells in the perfusate at single cell transcriptome level.
Renal injury, complement deposition, coagulation and human lymphocyte influx are all strongly reduced in genetically modified pig kidneys with
porcine MHC class I and three xenoantigens (GGTA1, CMAH, B4GALNT2) eliminated (4KO) compared to wildtype (WT) pig kidneys after 6-hours human
blood perfusion. Single cell RNA sequencing of endothelial cells (EC) from 4KO and WT pig kidneys respectively reveal that there is a compartment
(cortex, glomeruli and medulla)-specific endothelial activation, with cortical and glomeruli endothelial cells being more affected. Differential
gene expression analysis shows a downregulation of endothelial transcriptome activation response to human blood perfusion in the 4KO ECs. Pathway
enrichment analysis further identify the NF-kB pathway as strongly activated in human blood perfused WT ECs but diminished in the 4KO.
In conclusion, the 4KO pig model has strongly reduced endothelial activation and immune response when perfused with human whole blood.
Our data support further development of the 4KO for use in clinical transplantation.
Please cite the KPA as:
Citation will be updated.
Contact:
Yonglun Luo (Alun), Ph.D., Professor
Group leader, Department of Biomedicine, Aarhus University
The Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao
Email: alun@biomed.au.dk
Address: Building 1116-152, Hoegh-Guldbergs Gade 10, 8000 Aarhus
Blood Type Marker
Compartment Marker
Group_Compartment Marker
Vascular Bed Marker
Cell information vs gene expression on reduced dimensions
In this tab, users can visualise both cell information and gene
expression side-by-side on low-dimensional representions.
Cell information / gene expression violin plot / box plot
In this tab, users can visualise the gene expression or continuous cell information
(e.g. Number of UMIs / module score) across groups of cells (e.g. libary / clusters).
Proportion / cell numbers across different cell information
In this tab, users can visualise the composition of single cells based on one discrete
cell information across another discrete cell information.
Usage examples include the library or cellcycle composition across clusters.
In this tab, users can visualise the gene expression patterns of
multiple genes grouped by categorical cell information (e.g. library / cluster).
The normalised expression are averaged, log-transformed and then plotted.