Spatially resolved human kidney multi-omics single cell atlas highlights the key role of the fibrotic microenvironment in kidney disease progression

Cite

Abedini, A., Levinsohn, J., Klötzer, K.A., Dumoulin, B., Ma, Z., Frederick, J., Dhillon, P., Balzer, M.S., Shrestha, R., Liu, H. and Vitale, S., 2022. Spatially resolved human kidney multi-omics single cell atlas highlights the key role of the fibrotic microenvironment in kidney disease progression. Biorxiv, pp.2022-10.

https://doi.org/10.1101/2022.10.24.513598

Abstract

Kidneys possess one of the most intricate three-dimensional cellular structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. Here, we have generated high-quality datasets for 81 samples, including single cell (sc), single nuclear (sn), spot level (Visium) and single cell resolution (CosMx) spatial (sp)-RNA expression, and sn open chromatin, capturing cells from healthy, diabetic, and hypertensive diseased human kidneys. By combining the snRNA, snATAC and scRNA sequencing we identify cell types and map these cell types to their locations within the tissue. Unbiased deconvolution of the spatial data identifies 4 distinct spatial microenvironments: glomerular, immune, tubule and fibrotic. We describe the complex, heterogenous cellular and spatial organization of human microenvironments in health and disease. Further, we find that the fibrotic microenvironment spatial gene signature is not only able to molecularly classify human kidneys, but it also offers an improved prognosis prediction compared to traditional histopathological analysis. We provide a comprehensive spatially resolved molecular roadmap of the human kidney and the fibrotic process, demonstrating the clinical utility of spatial transcriptomics.

Datasets

1. Integrated human kidney sn/scRNAseq and snATACseq data

Explore
Assay
Sex
Cell type
Nucleosome group
Sample ID
Age
Disease
Disease group
Subject ID
Sample preservation method
Tissue
Reference genome
Age group
Leiden clustering
10X Chromium 3ʹ v3.1, single-nucleus155,647 cells
10X Chromium 3ʹ v3.1126,963 cells
10X Chromium snATAC55,955 cells
Spatially resolved human kidney multi-omics single cell atlas highlights the key role of the fibrotic microenvironment in kidney disease progression

2. Integrated human kidney data and kidney precision medicine project (KPMP)

Explore
Assay
Reference source
Library ID
Kidney region
Clustering (origin)
Sample type
Disease
Sex
Sampled site condition
Sample collection method
Cell type (origin)
Cell type
Sample source
Nucleosome group
Sample preservation method
Tissue
Reference genome
Leiden clustering
Age
Age group
Sample ID
Subject ID
10X Chromium 3ʹ v3.1, single-nucleus304,330 cells
10X Chromium 3ʹ v3.1229,374 cells
10X Chromium snATAC54,473 cells
Spatially resolved human kidney multi-omics single cell atlas highlights the key role of the fibrotic microenvironment in kidney disease progression

Alias names

GSE211785