An atlas of healthy and injured cell states and niches in the human kidney
Blue B. Lake, Rajasree Menon, Seth Winfree, Qiwen Hu, Ricardo Melo Ferreira, Kian Kalhor, Daria Barwinska, Edgar A. Otto, Michael Ferkowicz, Dinh Diep, Nongluk Plongthongkum, Amanda Knoten, Sarah Urata, Laura H. Mariani, Abhijit S. Naik, Sean Eddy, Bo Zhang, Yan Wu, Diane Salamon, James C. Williams, Xin Wang, Karol S. Balderrama, Paul J. Hoover, Evan Murray, Jamie L. Marshall, Teia Noel, Anitha Vijayan, Austin Hartman, Fei Chen, Sushrut S. Waikar, Sylvia E. Rosas, Francis P. Wilson, Paul M. Palevsky, Krzysztof Kiryluk, John R. Sedor, Robert D. Toto, Chirag R. Parikh, Eric H. Kim, Rahul Satija, Anna Greka, Evan Z. Macosko, Peter V. Kharchenko, Joseph P. Gaut, Jeffrey B. Hodgin, KPMP Consortium, Michael T. Eadon, Pierre C. Dagher, Tarek M. El-Achkar, Kun Zhang, Matthias Kretzler, Sanjay Jain
Abstract
Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.
Datasets
1. Integrated Single-nucleus and Single-cell RNA-seq of the Adult Human Kidney
Metadata
library
experiment
specimen
condition.long
condition.l1
condition.l2
donor_id
region.l1
region.l2
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disease_ontology_term_id
sex_ontology_term_id
development_stage_ontology_term_id
self_reported_ethnicity_ontology_term_id
eGFR
BMI
diabetes_history
hypertension
tissue_ontology_term_id
organism_ontology_term_id
assay_ontology_term_id
cell_type_ontology_term_id
suspension_type
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cell_type
assay
disease
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sex
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KPMP_20200702B_10X-R2891 cells BUKMAP_20200205F_10X-R2468 cells BUKMAP_20190829B_10X-R2444 cells BUKMAP_20191104A-10X-R2256 cells KPMP_20200212F_10X-R2098 cells BUKMAP_20200707A_10X-R2013 cells BUKMAP_20200707C_10X-R1678 cells KPMP_20190829C_10X-R1661 cells KPMP_20200212G_10X-R1301 cells BUKMAP_20200205D_10X-R1291 cells KPMP_20200212A_10X-R1256 cells KPMP_20191204B_10X-R352 cells BUKMAP_20191009-10X-R268 cells S-1910-000149_R113763 cells S-1908-010077_R18667 cells S-1908-000858_R18216 cells S-1909-007161_R17019 cells S-1910-000196_R16917 cells S-1908-009890_R16099 cells S-1908-000952-R16039 cells S-1908-009653_R15380 cells S-1908-000905_R15113 cells S-1908-009843_R14799 cells S-1908-010125_R14666 cells S-1910-000055_R13695 cells S-2001-000055_R12098 cells S-2001-000102_R11301 cells S-1908-010172_R11256 cells S-1905-017562-R1352 cells Normal Reference107701 cells Acute Kidney Injury (AKI)65171 cells Diabetic Kidney Disease (DKD)64429 cells Hypertensive CKD (H-CKD)39860 cells Chronic Kidney Disease7916 cells Deceased Donor19246 cells Adaptive / Maladaptive / Repairing Proximal Tubule Epithelial Cell26027 cells Degenerative Proximal Tubule Epithelial Cell25023 cells Cortical Thick Ascending Limb Cell23767 cells Proximal Tubule Epithelial Cell Segment 1 / Segment 217623 cells Adaptive / Maladaptive / Repairing Thick Ascending Limb Cell14924 cells Degenerative Medullary Thick Ascending Limb Cell11109 cells Degenerative Outer Medullary Collecting Duct Principal Cell9801 cells Peritubular Capilary Endothelial Cell 9195 cells Medullary Thick Ascending Limb Cell8876 cells Distal Convoluted Tubule Cell Type 17763 cells Cortical Collecting Duct Intercalated Cell Type A7673 cells Connecting Tubule Cell7024 cells Proximal Tubule Epithelial Cell Segment 36549 cells Medullary Fibroblast6138 cells Ascending Vasa Recta Endothelial Cell5132 cells Descending Thin Limb Cell Type 14700 cells Degenerative Distal Convoluted Tubule Cell4551 cells Monocyte-derived Cell4441 cells Cortical Collecting Duct Principal Cell4361 cells Inner Medullary Collecting Duct Cell4287 cells Descending Vasa Recta Endothelial Cell4286 cells Natural Killer Cell / Natural Killer T Cell4201 cells Macula Densa Cell4115 cells Connecting Tubule Principal Cell3975 cells Glomerular Capillary Endothelial Cell3764 cells Degenerative Cortical Thick Ascending Limb Cell3466 cells Vascular Smooth Muscle Cell / Pericyte3449 cells Intercalated Cell Type B3216 cells Degenerative Cortical Intercalated Cell Type A3194 cells Descending Thin Limb Cell Type 23130 cells Outer Medullary Collecting Duct Principal Cell2897 cells Non-classical Monocyte2435 cells Parietal Epithelial Cell2417 cells Ascending Thin Limb Cell2230 cells Degenerative Connecting Tubule Cell2178 cells Degenerative Inner Medullary Collecting Duct Cell1893 cells Outer Medullary Collecting Duct Intercalated Cell Type A1845 cells Afferent / Efferent Arteriole Endothelial Cell1705 cells Descending Thin Limb Cell Type 31550 cells Adaptive / Maladaptive / Repairing Fibroblast1516 cells Degenerative Vascular Smooth Muscle Cell1461 cells Transitional Principal-Intercalated Cell1409 cells Vascular Smooth Muscle Cell1233 cells Degenerative Ascending Thin Limb Cell1154 cells Distal Convoluted Tubule Cell Type 2827 cells Cycling Proximal Tubule Epithelial Cell809 cells Degenerative Medullary Fibroblast714 cells Connecting Tubule Intercalated Cell Type A664 cells Papillary Tip Epithelial Cell531 cells Degenerative Fibroblast469 cells Lymphatic Endothelial Cell463 cells Degenerative Podocyte412 cells Degenerative Descending Thin Limb Cell Type 3406 cells Degenerative Peritubular Capilary Endothelial Cell269 cells Degenerative Endothelial Cell236 cells Classical Dendritic Cell216 cells Cycling Mononuclear Phagocyte215 cells Cycling Natural Killer Cell / Natural Killer T Cell165 cells Cycling Endothelial Cell125 cells Renin-positive Juxtaglomerular Granular Cell106 cells Schwann Cell / Neural77 cells Cycling Distal Convoluted Tubule Cell75 cells Plasmacytoid Dendritic Cell75 cells Cycling Connecting Tubule Cell68 cells Cycling Myofibroblast66 cells adaptive - epi40951 cells epithelial cells228939 cells endothelial cells25175 cells proximal tubules76031 cells Distal tubules64549 cells Collecting tubules55016 cells intermediate tubules28094 cells renal corpuscle9471 cells MONDO:0005300112205 cells HsapDv:000024184310 cells HsapDv:000024244654 cells HsapDv:000024028404 cells HsapDv:000023821570 cells HsapDv:000017020400 cells HsapDv:000016011984 cells HsapDv:000015710807 cells HANCESTRO:0005201957 cells HANCESTRO:056855974 cells 30.0 and Above30398 cells UBERON:0001225122914 cells UBERON:0002113104314 cells UBERON:000036257086 cells UBERON:000122820338 cells NCBITaxon:9606304652 cells epithelial cell of proximal tubule76031 cells kidney loop of Henle thick ascending limb epithelial cell66257 cells endothelial cell25175 cells kidney collecting duct principal cell23239 cells kidney collecting duct intercalated cell18001 cells kidney interstitial fibroblast16548 cells kidney connecting tubule epithelial cell13245 cells kidney distal convoluted tubule epithelial cell13216 cells kidney loop of Henle thin descending limb epithelial cell9786 cells renal interstitial pericyte6707 cells mononuclear phagocyte4656 cells kidney interstitial alternatively activated macrophage3533 cells kidney loop of Henle thin ascending limb epithelial cell3384 cells non-classical monocyte2435 cells parietal epithelial cell2417 cells papillary tips cell531 cells conventional dendritic cell216 cells plasmacytoid dendritic cell, human75 cells chronic kidney disease112205 cells acute kidney failure84746 cells cortex of kidney122914 cells African American55974 cells Hispanic or Latin American8609 cells seventh decade human stage84310 cells eighth decade human stage44654 cells sixth decade human stage28404 cells fourth decade human stage21570 cells 76-year-old human stage20400 cells 66-year-old human stage11984 cells 63-year-old human stage10807 cells third decade human stage9555 cells 43-year-old human stage8609 cells 70-year-old human stage8084 cells 59-year-old human stage6488 cells 69-year-old human stage5151 cells 29-year-old human stage5105 cells 56-year-old human stage4952 cells 49-year-old human stage4232 cells 53-year-old human stage2952 cells 36-year-old human stage2891 cells 35-year-old human stage2635 cells 57-year-old human stage2627 cells 45-year-old human stage2468 cells 14-year-old human stage2256 cells 54-year-old human stage2013 cells 64-year-old human stage1661 cells 31-year-old human stage1631 cells 42-year-old human stage1540 cells 30-year-old human stage1334 cells 52-year-old human stage1329 cells 41-year-old human stage1166 cells fifth decade human stage988 cells 39-year-old human stage962 cells 47-year-old human stage740 cells 40-year-old human stage635 cells 48-year-old human stage519 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/bcb61471-2a44-4d00-a0af-ff085512674c
Alias names
KPMP, GSE183279, GSE169285, PMID37468583, PMC10356613
Cite this study
Lake, B.B., Menon, R., Winfree, S., Hu, Q., Melo Ferreira, R., Kalhor, K., Barwinska, D., Otto, E.A., Ferkowicz, M., Diep, D. and Plongthongkum, N., 2023. An atlas of healthy and injured cell states and niches in the human kidney. Nature, 619(7970), pp.585-594. https://doi.org/10.1038/s41586-023-05769-3
