An atlas of healthy and injured cell states and niches in the human kidney

Cite

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

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

Explore
Sample ID
Experiment
Specimen ID
Disease
Disease (level 1)
Disease (level 2)
Subject ID
Tissue region (level 1)
Tissue region (level 2)
Percent of cortex
Percent of medulla
Sample tissue type
Sample source
Cell type
Cell type (subclass l3)
Cell type (subclass l2)
Cell type (subclass l1)
State l2
State
Cell type (class)
Structure
eGFR
BMI
Diabetes history
Hypertension
Assay
Sex
Tissue
Ethnicity
Age
Age group
Leiden clustering
KB813,763 cells
KB58,667 cells
KBCVD38,609 cells
KB48,216 cells
KC797,775 cells
KC787,481 cells
KB77,019 cells
KB166,917 cells
PA36,488 cells
763-EO-16,110 cells
KB136,099 cells
PA46,089 cells
KB16,039 cells
KM1035,815 cells
KC335,744 cells
KM1025,652 cells
KC345,520 cells
573-EO-25,463 cells
KB35,380 cells
KB105,113 cells
269-EO-14,953 cells
KBCVD14,885 cells
KC394,837 cells
KB114,799 cells
KC774,765 cells
KC824,718 cells
2318-EO-24,690 cells
KB124,666 cells
1119-EO-24,333 cells
613-EO-24,173 cells
2318-EO-34,121 cells
1117-EO-24,053 cells
1120-EO-23,936 cells
763-EO-33,858 cells
KM693,730 cells
KB63,695 cells
1121-EO-23,634 cells
KC843,473 cells
345-EO-33,239 cells
dKC33,199 cells
KBCVD23,190 cells
dKC23,056 cells
1120-EO-12,996 cells
KC352,962 cells
573-EO-12,944 cells
KBCVD42,891 cells
2318-EO-12,834 cells
1121-EO-32,667 cells
763-EO-22,666 cells
622-EO-22,617 cells
KM722,468 cells
KC362,444 cells
269-EO-22,396 cells
KC402,256 cells
622-EO-12,225 cells
763-EO-42,153 cells
KB142,098 cells
KC832,013 cells
1117-EO-11,724 cells
PA51,678 cells
dKC11,661 cells
PRE0271,631 cells
PRE0381,540 cells
613-EO-11,426 cells
PRE98sc1,336 cells
1153EO-31,334 cells
1162EO-21,329 cells
PRE019-41,323 cells
KB151,301 cells
KM711,291 cells
KB91,256 cells
1157EO-21,166 cells
1121-EO-11,145 cells
1119-EO-11,104 cells
1157EO-11,042 cells
PRE19-025994 cells
141361988 cells
PRE018-1963 cells
1162EO-1962 cells
593-EO-1960 cells
1158EO-3958 cells
1158EO-2933 cells
1153EO-2844 cells
1153EO-1833 cells
1157EO-3740 cells
PRE19-05635 cells
PRE062-1635 cells
1158EO-1519 cells
PRE055-1517 cells
1120-EO-3460 cells
KB2352 cells
PA1268 cells
593-EO-2212 cells
An atlas of healthy and injured cell states and niches in the human kidney

2. Single-nucleus RNA-seq of the Adult Human Kidney (Version 1.0)

Explore
Sample ID
Experiment
Specimen ID
Disease
Disease (level 1)
Disease (level 2)
Subject ID
Tissue region (level 1)
Tissue region (level 2)
Percent of cortex
Percent of medulla
Sample tissue type
Sample source
Cell type
Cell type (subclass l3)
Cell type (subclass l2)
Cell type (subclass l1)
State l2
State
Cell type (class)
Structure
eGFR
BMI
Diabetes history
Hypertension
Assay
Sex
Tissue
Ethnicity
Age
Age group
Leiden clustering
KB813,763 cells
KB58,667 cells
KB48,216 cells
KC797,775 cells
KC787,481 cells
KB77,019 cells
KB166,917 cells
PA36,488 cells
KB136,099 cells
PA46,089 cells
KB16,039 cells
KM1035,815 cells
KC335,744 cells
KM1025,652 cells
KC345,520 cells
KB35,380 cells
KB105,113 cells
KC394,837 cells
KB114,799 cells
KC774,765 cells
KC824,718 cells
KB124,666 cells
KM693,730 cells
KB63,695 cells
KC843,473 cells
KC352,962 cells
KM722,468 cells
KC362,444 cells
KC402,256 cells
KB142,098 cells
KC832,013 cells
PA51,678 cells
KB151,301 cells
KM711,291 cells
KB91,256 cells
KB2352 cells
PA1268 cells
An atlas of healthy and injured cell states and niches in the human kidney

3. Single-cell RNA-seq of the Adult Human Kidney (Version 1.0)

Explore
Tissue region (level 2)
Tissue region (level 1)
Data source
Sample type
Clustering
Tissue type
Cell type (subclass)
eGFR
BMI
Diabetes history
Hypertension
Specimen ID
Subject ID
Sex
Ethnicity
Age
Sample ID
Experiment
Disease
Disease (level 1)
Disease (level 2)
Percent of cortex
Percent of medulla
Sample tissue type
Sample source
Cell type
Cell type (subclass l3)
Cell type (subclass l2)
Cell type (subclass l1)
State l2
State
Cell type (class)
Structure
Assay
Tissue
Age group
Leiden clustering
C-TAL15,036 cells
aPT9,707 cells
PT-S1/S26,787 cells
aTAL26,523 cells
dPT5,705 cells
PC4,664 cells
T4,264 cells
EC-PTC4,089 cells
IC-A3,284 cells
DCT13,126 cells
dCNT-PC3,082 cells
CNT3,068 cells
dPT/DTL2,394 cells
dPC2,274 cells
CNT-IC-A1,977 cells
dCNT1,850 cells
dC-TAL1,812 cells
EC-AEA1,706 cells
cDC1,684 cells
DTL11,653 cells
tPC-IC1,649 cells
dDCT1,553 cells
EC-GC1,405 cells
MON1,322 cells
MDC1,318 cells
NKT1,246 cells
VSMC/P1,196 cells
B1,125 cells
M-TAL1,053 cells
aTAL11,008 cells
T-CYT915 cells
MAC-M2879 cells
dVSMC830 cells
NK1774 cells
FIB687 cells
IC-B649 cells
PEC623 cells
CNT-PC547 cells
dIC-A425 cells
PL406 cells
ncMON364 cells
dEC-PTC258 cells
POD242 cells
T-REG238 cells
cycT231 cells
cycEPI218 cells
cycMNP206 cells
pDC206 cells
NK2203 cells
PT-S3174 cells
aFIB173 cells
REN163 cells
MC130 cells
EC-LYM103 cells
MyoF73 cells
cycEC39 cells
MAST28 cells
An atlas of healthy and injured cell states and niches in the human kidney

4. Patient 20-576 [Slide-seq2]

Explore
Cell type
Cell type (level 2)
Sample ID
Leiden clustering
Subject ID
Specimen ID
Assay
Disease
Tissue annotation (level 1)
Tissue annotation (level 2)
Sex
Tissue type
Sample source
Tissue
Reference genome
Age group
l1.TAL36,176 cells
l1.FIB27,880 cells
l1.PT26,903 cells
l1.TL14,343 cells
l1.EC12,244 cells
l1.IMM10,698 cells
l1.PC7,701 cells
l1.VSM/P7,031 cells
l1.IC6,733 cells
l1.DCT5,025 cells
l1.CNT4,998 cells
l1.POD4,488 cells
l1.PEC2,883 cells
An atlas of healthy and injured cell states and niches in the human kidney

5. Patient 21-019 [Slide-seq2]

Explore
Cell type
Cell type (level 2)
Sample ID
Leiden clustering
Specimen ID
Assay
Disease
Subject ID
Tissue annotation level 1
Tissue annotation level 2
Sex
Tissue type
Sample source
GEO accession
Reference genome
Age group
Tissue
l1.TAL51,878 cells
l1.PT46,844 cells
l1.TL24,850 cells
l1.FIB21,849 cells
l1.EC15,998 cells
l1.IMM12,869 cells
l1.PC12,485 cells
l1.VSM/P11,311 cells
l1.DCT8,338 cells
l1.IC6,582 cells
l1.CNT3,846 cells
l1.PEC3,553 cells
l1.POD2,472 cells
An atlas of healthy and injured cell states and niches in the human kidney

6. Patient 21-020 [Slide-seq2]

Explore
Cell type
Cell type (level 2)
Sample ID
Leiden clustering
Specimen ID
Assay
Subject ID
Tissue annotation level 1
Tissue annotation level 2
Sex
Tissue type
Sample source
GEO accession
Reference genome
Age group
Tissue
Disease
l1.PT57,702 cells
l1.FIB30,688 cells
l1.TAL27,275 cells
l1.IMM24,348 cells
l1.EC23,963 cells
l1.PC18,076 cells
l1.TL15,052 cells
l1.VSM/P11,174 cells
l1.POD5,719 cells
l1.IC4,686 cells
l1.DCT3,858 cells
l1.CNT2,848 cells
l1.PEC2,275 cells
An atlas of healthy and injured cell states and niches in the human kidney

7. Patient 3579 [Slide-seq2]

Explore
Cell type
Cell type (level 2)
Sample ID
Leiden clustering
Specimen ID
Assay
Subject ID
Tissue annotation level 1
Tissue annotation level 2
Sex
Race
Tissue type
Sample source
Source ID
Reference genome
Age group
Tissue
Disease
l1.PT121,878 cells
l1.TAL28,673 cells
l1.EC17,999 cells
l1.IMM14,149 cells
l1.DCT13,788 cells
l1.FIB10,529 cells
l1.CNT8,512 cells
l1.POD7,174 cells
l1.VSM/P6,556 cells
l1.PC6,473 cells
l1.IC4,608 cells
l1.PEC4,043 cells
l1.TL1,731 cells
An atlas of healthy and injured cell states and niches in the human kidney

8. Patient 3593 [Slide-seq2]

Explore
Cell type
Cell type (level 2)
Sample ID
Leiden clustering
Specimen ID
Assay
Subject ID
Tissue annotation level 1
Tissue annotation level 2
Sex
Race
Donor living at sample collection
Sample source
Source ID
Reference genome
Age group
Tissue
Disease
l1.TL71,411 cells
l1.TAL68,201 cells
l1.PC41,929 cells
l1.EC39,912 cells
l1.FIB26,427 cells
l1.PT11,134 cells
l1.IC5,932 cells
l1.IMM5,120 cells
l1.VSM/P4,402 cells
l1.PEC2,212 cells
l1.CNT1,603 cells
l1.DCT1,580 cells
l1.POD380 cells
An atlas of healthy and injured cell states and niches in the human kidney

9. Patient 3611 [Slide-seq2]

Explore
Cell type
Cell type (level 2)
Sample ID
Leiden clustering
Specimen ID
Assay
Subject ID
Tissue annotation level 1
Tissue annotation level 2
Sex
Race
Tissue type
Sample source
Source ID
Reference genome
Age group
Tissue
Disease
l1.TAL87,046 cells
l1.EC51,340 cells
l1.TL45,631 cells
l1.PC43,437 cells
l1.FIB40,861 cells
l1.IC13,245 cells
l1.VSM/P11,967 cells
l1.IMM8,091 cells
l1.PT6,652 cells
l1.PEC3,216 cells
l1.DCT2,742 cells
l1.CNT2,526 cells
l1.POD832 cells
An atlas of healthy and injured cell states and niches in the human kidney

10. Spatial localization with Spatial Transcriptomics for an atlas of healthy and injured cell states and niches in the human kidney [Visium ST]

Explore
Sample ID
Specimen ID
Assay
Disease
Disease (level 1)
Disease (level 2)
Subject ID
Tissue annotation
Sex
Race
Tissue type
Sample source
Source ID
Tissue
Reference genome
Sample preservation method
Leiden clustering
eGFR
Age group
Age
BMI
V19S25-019_XY03-M614,166 cells
V19S25-019_XY04-F523,627 cells
V19S25-019_XY02-M322,627 cells
V19S25-017_XY03-134371,322 cells
V10S15-102_XY02_IU-21-019-51,034 cells
V10S15-102_XY03_IU-21-015-2956 cells
V10S14-086_XY03_21-0063904 cells
V10S14-086_XY01_21-0055787 cells
V10S14-085_XY03_21-0056673 cells
V10S21-388_XY04_20-0073673 cells
V10S21-388_XY03_20-0072673 cells
V10S14-085_XY02_20-0040645 cells
V10S14-086_XY04_21-0066640 cells
V10S14-086_XY02_20-0039601 cells
V10S21-388_XY01_21-0068560 cells
V10S14-087_XY03_21-0064534 cells
V10S14-087_XY04_21-0065507 cells
V10S14-087_XY02_21-0063461 cells
V10S14-087_XY01_21-0061453 cells
V10S14-085_XY04_21-0057407 cells
V10S21-388_XY02_20-0071370 cells
V10S14-085_XY01_20-0038317 cells
An atlas of healthy and injured cell states and niches in the human kidney

11. An atlas of healthy and injured cell states and niches in the human kidney [SNARE-Seq2]

Explore
Library ID
Doublet detection
Sample ID
Experiment
Specimen ID
Disease
Subject ID
Tissue region (level 1)
Tissue region (level 2)
Tissue region (level 3)
Sex
Race
Tissue type
Assay
Sample source
Cell type (predicted class)
Cell type (predicted subclass l1)
Cell type
Cell type (subclass l3)
Cell type (subclass l2)
Cell type (subclass l1)
State (level 2)
State (level 1)
Cell type (class)
Structure
Tissue
Leiden clustering
Sample preservation method
Reference genome
Age group
KC512,928 cells
KC742,656 cells
KM942,610 cells
KC472,325 cells
KC482,267 cells
KC692,182 cells
KC492,180 cells
KC682,111 cells
KC702,090 cells
KC452,079 cells
KC462,059 cells
KC672,057 cells
KM902,027 cells
KM872,023 cells
KM881,999 cells
KM891,983 cells
KM911,980 cells
KM671,970 cells
KC731,949 cells
KC711,949 cells
KM631,925 cells
KM651,897 cells
KM551,884 cells
KM621,872 cells
KC721,852 cells
KM931,794 cells
KM921,741 cells
KM501,706 cells
KM531,654 cells
KM511,629 cells
KM661,591 cells
KC241,527 cells
KC231,471 cells
KC261,439 cells
KM541,406 cells
KM471,358 cells
KM451,312 cells
KM491,306 cells
KC221,262 cells
KM481,253 cells
KM441,182 cells
KC211,149 cells
KM381,149 cells
KM28974 cells
KM31959 cells
KM86948 cells
KM79864 cells
KM29855 cells
KM84753 cells
KM82737 cells
KM83720 cells
KM59715 cells
KM27704 cells
KM26702 cells
KM80699 cells
KM81659 cells
KM73658 cells
KM77636 cells
KM75632 cells
KM57630 cells
KM61630 cells
KC66626 cells
KM56611 cells
KM76608 cells
KM74600 cells
KM60560 cells
KC60538 cells
KC61535 cells
KC62511 cells
KC63508 cells
KC58504 cells
KC59482 cells
KC65479 cells
KC64452 cells
KC55430 cells
KM30430 cells
KC56422 cells
KC54407 cells
KC53373 cells
KC52367 cells
KM101365 cells
KM99290 cells
KM98274 cells
KM96243 cells
KM97241 cells
KM95235 cells
KM23185 cells
KM25185 cells
KM24164 cells
KM21151 cells
KM20128 cells
KC25112 cells
KM6483 cells
KM1964 cells
KM1762 cells
KM1855 cells
KC5051 cells
KM1547 cells
KM5846 cells
KM5230 cells
KM1428 cells
KM2220 cells
KC5716 cells
KM1009 cells
KM468 cells
KM857 cells
KM165 cells
KM784 cells
An atlas of healthy and injured cell states and niches in the human kidney

Alias names

GSE183279, GSE183273, GSE183274, GSE183276, GSE183277, GSE183456, GSE199711