The chromatin landscape of healthy and injured cell types in the human kidney

Debora L. Gisch; Michelle Brennan; Blue B. Lake; Jeannine M. Basta; Mark S. Keller; Ricardo Melo Ferreira; Shreeram Akilesh; Reetika R. Ghag; Charles Lu; Yinghua Cheng; Kimberly S. Collins; Samir V. Parikh; Brad Harris Rovin; Lynn Robbins; Lisa Stout; Kimberly Y. Conklin; Dinh H. Diep; Bo Zhang; Amanda L. Knoten; Daria Barwinska; Mahla Asghari; Angela R. Sabo; Michael J. Ferkowicz; Timothy Alan Sutton; Katherine J. Kelly; Ian H. de Boer; Sylvia Eleni Rosas; Krzysztof Kiryluk; Jeffrey B. Hodgin; Fadhl M. AlAkwaa; Aydin Türkmen; Joseph P. Gaut; Nils Gehlenborg; Carrie L. Phillips; Tarek Maurice El-Achkar; Pierre C. Dagher; Takeshi Hato; Kun Zhang; Jonathan Himmelfarb; Matthias Kretzler; Shamim Ara Mollah; Alexander Morales; Isaac Ely Stillman; Stewart H. Lecker; Steven A. Bogen; Ashish Verma; Guanghao Yu; Insa Marie Schmidt; Joel M. Henderson; Laurence H. Beck; Pranav Yadati; Sushrut S. Waikar; Afolarin A. Amodu; Shana Maikhor; Titilayo O. Ilori; Mia R. Colona; Astrid Weins; Gearoid Michael McMahon; Nir Hacohen; Anna Greka; Jamie L. Marshall; Paul J. Hoover; Vidya S. Viswanathan; Dana C. Crawford; Mark P. Aulisio; William S. Bush; Yijiang M. Chen; Anant Madabhushi; Charles M. O’Malley; Crystal Ann Gadegbeku; Dianna Sendrey; Emilio D. Poggio; John F. O’Toole; John R. Sedor; Jonathan J. Taliercio; Lakeshia Bush; Leal C. Herlitz; Ellen Palmer; Jane Kim Nguyen; Kassandra Spates-Harden; Leslie Cooperman; Stacey E. Jolly; Carissa Vinovskis; Andrew S. Bomback; Jonathan M. Barasch; Paul S. Appelbaum; D; David H. Beyda

doi:10.1038/s41467-023-44467-6

Journal article

The chromatin landscape of healthy and injured cell types in the human kidney

Debora L. Gisch, Michelle Brennan, Blue B. Lake, Jeannine M. Basta, Mark S. Keller, Ricardo Melo Ferreira, Shreeram Akilesh, Reetika R. Ghag, Charles Lu, Yinghua Cheng, …

Nature Communications, Vol.15(1)

2024

DOI: https://doi.org/10.1038/s41467-023-44467-6

Abstract

elf3 protein

histone H3

kruppel like factor 10

kruppel like factor 6

nr2f1 protein

nuclear RNA

transcription factor

unclassified drug

cell

DNA

gene expression

injury

limb

protein

RNA

Article

cell damage

cell specificity

chromatin

controlled study

DNA methylation

epigenetics

gene activation

gene control

gene regulatory network

gene repression

genome

histone modification

human

human cell

human tissue

kidney cell

proximal tubule cell

target cell

cell count

genetics

health status

kidney

kidney proximal tubule

Cell Count

Chromatin

Health Status

Humans

Kidney

Kidney Tubules, Proximal

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. © 2024, The Author(s).

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Title: The chromatin landscape of healthy and injured cell types in the human kidney
Creators: Debora L. Gisch - Indiana University – Purdue University Indianapolis
Michelle Brennan - Saint Louis University
Blue B. Lake - University of California San Diego
Jeannine M. Basta - Washington University in St. Louis
Mark S. Keller - Harvard University
Ricardo Melo Ferreira
Shreeram Akilesh - University of Washington Applied Physics Laboratory
Reetika R. Ghag - Washington University in St. Louis
Charles Lu - Washington University in St. Louis
Yinghua Cheng
Kimberly S. Collins - Indiana University – Purdue University Indianapolis
Samir V. Parikh - The Ohio State University Wexner Medical Center
Brad Harris Rovin - The Ohio State University Wexner Medical Center
Lynn Robbins
Lisa Stout - Washington University in St. Louis
Kimberly Y. Conklin - University of California San Diego
Dinh H. Diep - University of California San Diego
Bo Zhang - Washington University in St. Louis
Amanda L. Knoten - Washington University in St. Louis
Daria Barwinska - Indiana University – Purdue University Indianapolis
Mahla Asghari - Indiana University School of Medicine
Angela R. Sabo - Indiana University – Purdue University Indianapolis
Michael J. Ferkowicz - Indiana University School of Medicine
Timothy Alan Sutton - Indiana University – Purdue University Indianapolis
Katherine J. Kelly - Indiana University School of Medicine
Ian H. de Boer - University of Washington Applied Physics Laboratory
Sylvia Eleni Rosas - Joslin Diabetes Center
Krzysztof Kiryluk - Columbia University
Jeffrey B. Hodgin - University of Michigan
Fadhl M. AlAkwaa - University of Michigan
Aydin Türkmen - Istanbul University
Joseph P. Gaut - University of California San Diego
Nils Gehlenborg - Harvard University
Carrie L. Phillips - Indiana University – Purdue University Indianapolis
Tarek Maurice El-Achkar - Indiana University – Purdue University Indianapolis
Pierre C. Dagher - Indiana University School of Medicine
Takeshi Hato
Kun Zhang - University of California San Diego
Jonathan Himmelfarb - University of Washington Applied Physics Laboratory
Matthias Kretzler - University of Michigan
Shamim Ara Mollah - Washington University in St. Louis
Alexander Morales - Altos Labs
Isaac Ely Stillman - Beth Israel Deaconess Medical Center
Stewart H. Lecker - Beth Israel Deaconess Medical Center
Steven A. Bogen
Ashish Verma - Boston Medical Center
Guanghao Yu - Boston Medical Center
Insa Marie Schmidt - Boston Medical Center
Joel M. Henderson - Boston Medical Center
Laurence H. Beck - Boston Medical Center
Pranav Yadati - Boston Medical Center
Sushrut S. Waikar - Boston Medical Center
Afolarin A. Amodu - Boston Medical Center
Shana Maikhor - Boston Medical Center
Titilayo O. Ilori
Mia R. Colona - Boston Medical Center
Astrid Weins - Brigham and Women's Hospital
Gearoid Michael McMahon - Brigham and Women's Hospital
Nir Hacohen - Brigham and Women's Hospital
Anna Greka - Broad Institute
Jamie L. Marshall - Broad Institute
Paul J. Hoover - Broad Institute
Vidya S. Viswanathan - Broad Institute
Dana C. Crawford - Case Western Reserve University
Mark P. Aulisio - Case Western Reserve University
William S. Bush - Case Western Reserve University
Yijiang M. Chen - Case Western Reserve University
Anant Madabhushi - Case Western Reserve University
Charles M. O’Malley - Cleveland Clinic
Crystal Ann Gadegbeku - Cleveland Clinic
Dianna Sendrey - Cleveland Clinic
Emilio D. Poggio - Cleveland Clinic
John F. O’Toole - Cleveland Clinic
John R. Sedor - Cleveland Clinic
Jonathan J. Taliercio - Cleveland Clinic
Lakeshia Bush - Cleveland Clinic
Leal C. Herlitz - Cleveland Clinic
Ellen Palmer - Cleveland Clinic
Jane Kim Nguyen - Cleveland Clinic
Kassandra Spates-Harden - Cleveland Clinic
Leslie Cooperman - Cleveland Clinic
Stacey E. Jolly - Cleveland Clinic
Carissa Vinovskis - Cleveland Clinic
Andrew S. Bomback - Columbia University
Jonathan M. Barasch - Columbia University
Paul S. Appelbaum - Columbia University
D
David H. Beyda
Publication Details: Nature Communications, Vol.15(1)
Publisher: Nature Research
Identifiers: 991006253071802656
Language: English
Resource Type: Journal article