ArticleNature communications2024
The chromatin landscape of healthy and injured cell types in the human kidney.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
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Who cites it
35 citing papers in PubMed, 35 citations in OpenAlex.
- Single-Nucleus Transcriptomic Atlas Reveals Disease-Associated Cellular States in Human Glomerular Diseases.Kidney international reports · 2026Article
- A cross-species single-cell kidney epigenome atlas reveals epithelial-dominant aging-like states in disease.Nature aging · 2026Article
- Inherited Susceptibility to Urinary Tract Infections from Kidney Papilla to Bladder.medRxiv : the preprint server for health sciences · 2026Article
- ELF3 links kidney function GWAS loci to maladaptive epithelial inflammation.Science advances · 2026Article
- A MEF2C transcription factor network regulates proliferation of glomerular endothelial cells in diabetic kidney disease.Kidney international · 2026Article
- Epigenetics-mediated pathological alterations and their diagnostic and therapeutic potential in sepsis-associated acute kidney injury.Clinical epigenetics · 2026Review
- DigitAb: Domain-Adaptive Cell Type Prediction Method from Light Microscopy Images.bioRxiv : the preprint server for biology · 2026Article
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Single-cell Stereo-seq reveals regulatory mechanisms driving regeneration of injured proximal tubules during AKI.Nature communications · 2026Article
- Hypoxia inducible factor network reflects kidney disease progression in diabetes and sodium-glucose co-transporters inhibition.Signal transduction and targeted therapy · 2026Article
- The response to kidney injury is epigenetically regulated through the activation of bivalent genes.American journal of physiology. Renal physiology · 2026Article
- Uncovering hidden risks: metabolic and inflammatory insights in normoalbuminuric chronic kidney disease.International urology and nephrology · 2026Article
- High-Efficiency Genomic Mapping of Chromatin-Associated Targets with CUT&RUN.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Chromatin remodeling and epigenetic regulation in chronic kidney disease.Frontiers in genetics · 2026Review
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- A Holistic Approach to AKI: Integrating Clinical and Molecular Data in the Human Kidney.Seminars in nephrology · 2025Review
- Single-cell epigenetics and multiomics analysis in kidney research.Clinical and experimental nephrology · 2025Review
- Single cell transcription revealing key transcription factors in embryonic kidney development.Molecular and cellular biochemistry · 2025Article
- Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules.Science advances · 2025Article
Corrections and comments
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Authors and funding
47 authors at 20 institutions in 3 countries.
Debora L Gisch *Indiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0001-9087-4585
Michelle Brennan *Saint Louis University, St. Louis, MO, 63103, USA.ORCID 0000-0002-3460-5599
Blue B Lake *Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0002-8637-9044
Jeannine Basta *Washington University in Saint Louis, St. Louis, MO, 63103, USA.
Mark S KellerHarvard Medical School, Boston, MA, 02142, USA.ORCID 0000-0003-3003-874X
Ricardo Melo FerreiraIndiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0003-2063-9744
Shreeram AkileshUniversity of Washington -, Seattle, WA, 98195, USA.
Reetika GhagWashington University in Saint Louis, St. Louis, MO, 63103, USA.
Charles LuWashington University in Saint Louis, St. Louis, MO, 63103, USA.
Ying-Hua ChengIndiana University School of Medicine, Indianapolis, IN, 46202, USA.
Kimberly S CollinsIndiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0002-4978-4593
Samir V ParikhOhio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Brad H RovinOhio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Lynn RobbinsSt. Louis Veteran Affairs Medical Center, St. Louis, MO, 63106, USA.
Lisa StoutWashington University in Saint Louis, St. Louis, MO, 63103, USA.
Kimberly Y ConklinDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Dinh DiepDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Bo ZhangWashington University in Saint Louis, St. Louis, MO, 63103, USA.ORCID 0000-0001-8895-2206
Amanda KnotenWashington University in Saint Louis, St. Louis, MO, 63103, USA.
Daria BarwinskaIndiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0002-0776-3030
Mahla AsghariIndiana University School of Medicine, Indianapolis, IN, 46202, USA.
Angela R SaboIndiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0002-7496-8570
Michael J FerkowiczIndiana University School of Medicine, Indianapolis, IN, 46202, USA.
Timothy A SuttonIndiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0002-4117-1434
Katherine J KellyIndiana University School of Medicine, Indianapolis, IN, 46202, USA.
Ian H De BoerUniversity of Washington -, Seattle, WA, 98195, USA.
Sylvia E RosasJoslin Diabetes Center, Harvard Medical School, Boston, MA, 02215, USA.
Krzysztof KirylukColumbia University, New York, NY, 10032, USA.ORCID 0000-0002-5047-6715
Jeffrey B HodginUniversity of Michigan, Ann Arbor, MI, 48109, USA.ORCID 0000-0003-0534-3048
Fadhl AlakwaaUniversity of Michigan, Ann Arbor, MI, 48109, USA.
Seth WinfreeUniversity of Nebraska Medical Center, Omaha, NE, 68198, USA.ORCID 0000-0002-2396-5871
Nichole JeffersonKidney Precision Medicine Project Community Engagement Committee, Dallas, TX, USA.
Aydın TürkmenIstanbul School of Medicine, Division of Nephrology, Istanbul, Turkey.
Joseph P GautDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Nils GehlenborgHarvard Medical School, Boston, MA, 02142, USA.ORCID 0000-0003-0327-8297
Carrie L PhillipsIndiana University School of Medicine, Indianapolis, IN, 46202, USA.
Tarek M El-AchkarIndiana University School of Medicine, Indianapolis, IN, 46202, USA.
Pierre C DagherIndiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0003-3321-5561
Takashi HatoIndiana University School of Medicine, Indianapolis, IN, 46202, USA.ORCID 0000-0002-0446-6575
Kun ZhangDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, USA.ORCID 0000-0002-7596-5224
Jonathan HimmelfarbUniversity of Washington -, Seattle, WA, 98195, USA.
Matthias KretzlerUniversity of Michigan, Ann Arbor, MI, 48109, USA.
Shamim MollahWashington University in Saint Louis, St. Louis, MO, 63103, USA.ORCID 0000-0001-9178-8339
Kidney Precision Medicine Project (KPMP)
Sanjay JainWashington University in Saint Louis, St. Louis, MO, 63103, USA. sanjayjain@wustl.edu.ORCID 0000-0003-2804-127X
Michael RauchmanWashington University in Saint Louis, St. Louis, MO, 63103, USA. mrauchma@wustl.edu.ORCID 0000-0002-4820-3689
Michael T EadonIndiana University School of Medicine, Indianapolis, IN, 46202, USA. meadon@iupui.edu.ORCID 0000-0003-3066-2876
University of Washington · USIndiana University School of MedicineUniversity of Michigan · USWashington University in St. Louis · USThe University of Texas Southwestern Medical Center · USCleveland Clinic · USColumbia University · USUniversity of Minnesota · USMount Sinai Medical Center · USUniversity of Illinois Chicago · USUniversity of Arizona · USBoston Medical Center · USUniversity of Pittsburgh · USVanderbilt University · USThe University of Texas Health Science Center at San Antonio · USJohns Hopkins University · USJoslin Diabetes Center · USKPMG (United States) · USYale University · USUniversity of North Carolina at Chapel Hill · US
Funding
SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5MCentral Hub for Kidney Precision MedicineU24DK114886 · NIDDK · UNIVERSITY OF WASHINGTON · PI Jonathan Himmelfarb, Matthias Kretzler · 2022 to 2026
$21.1MTraining Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8MKPMP Kidney Mapping and Atlas Project (KMAP)U01DK133090 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jonathan Himmelfarb, Matthias Kretzler · 2022 to 2026
$10.4MKidney single cell and spatial molecular atlas project - KIDSSMAPU54DK134301 · NIDDK · WASHINGTON UNIVERSITY · PI JAIN, SANJAY · 2022 to 2025
$7.8MIntegrated spatial interrogation of cellular and molecular signatures of human kidney diseaseU01DK114923 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Tarek Maurice Ashkar, Pierre C Dagher · 2022 to 2026
$5.4MSingle cell multiomic and spatial atlas of acute and chronic kidney injuryU01DK114933 · NIDDK · WASHINGTON UNIVERSITY · PI Sanjay Jain · 2022 to 2026
$5.0MResearch Project 2: Molecular analysis of developing post-natal mouse kidney in health and FSGSP50DK133943 · NIDDK · WASHINGTON UNIVERSITY · PI Carmen M. Halabi, Sanjay Jain · 2022 to 2026
$4.9MResource Development CoreU54DK137328 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI KENNETH W DUNN · 2023 to 2026
$4.5MEndotoxin preconditioning as a model to uncover protective pathways in sepsis-induced renal injury.R01DK107623 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Pierre C Dagher · 2016 to 2026
$4.4MSpatial Multi-Omics to Profile Metabolic Pathways for Kidney DiseaseU01DK114920 · NIDDK · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Christopher R Anderton, Kumar Sharma · 2022 to 2026
$3.9MBoston Chronic Kidney Disease Research Biopsy CenterU01DK133092 · NIDDK · BOSTON MEDICAL CENTER · PI Sylvia E Rosas, Sushrut S. Waikar · 2022 to 2026
$3.5MNCCIH NIH HHS R01 AT011463NHGRI NIH HHS T32 HG002295NIDDK NIH HHS P30 DK036836NIDDK NIH HHS P50 DK133943NIDDK NIH HHS R01 DK107623NIDDK NIH HHS R01 DK129879NIDDK NIH HHS U01 DK114866NIDDK NIH HHS U01 DK114907NIDDK NIH HHS U01 DK114908NIDDK NIH HHS U01 DK114920NIDDK NIH HHS U01 DK114923NIDDK NIH HHS U01 DK114933NIDDK NIH HHS U01 DK133081NIDDK NIH HHS U01 DK133090NIDDK NIH HHS U01 DK133091NIDDK NIH HHS U01 DK133092NIDDK NIH HHS U01 DK133093NIDDK NIH HHS U01 DK133095NIDDK NIH HHS U01 DK133097NIDDK NIH HHS U01 DK133113NIDDK NIH HHS U01 DK133766NIDDK NIH HHS U01 DK133768NIDDK NIH HHS U24 DK114886NIDDK NIH HHS U54 DK134301NIDDK NIH HHS U54 DK137328NIDDK NIH HHS UG3 DK114861NIDDK NIH HHS UH3 DK114861NIDDK NIH HHS UH3 DK114933NIH HHS S10 OD026880NIH HHS S10 OD030463
Abstract
There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney's active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.
Indexed as
ChromatinKidneyCell CountHealth StatusHumansKidney Tubules, ProximalChromatin
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