{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:06:45Z","timestamp":1793239605103,"version":"4.5.0"},"reference-count":80,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK123097"],"award-info":[{"award-number":["R01 DK123097"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30 DK114857"],"award-info":[{"award-number":["P30 DK114857"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001463","name":"American Society of Nephrology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001463","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20POST35210465"],"award-info":[{"award-number":["20POST35210465"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007263","name":"Astellas Foundation for Research on Metabolic Disorders","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007263","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, we show that proximal tubular (PT) cells develop a molecularly distinct, pro-inflammatory state following injury. While these inflammatory PT cells transiently appear after mild injury and return to their original state without inducing fibrosis, after severe injury they accumulate and contribute to persistent inflammation. This transient inflammatory PT state significantly downregulates glutathione metabolism genes, making the cells vulnerable to ferroptotic stress. Genetic induction of high ferroptotic stress in these cells after mild injury leads to the accumulation of the inflammatory PT cells, enhancing inflammation and fibrosis. Our study broadens the roles of ferroptotic stress from being a trigger of regulated cell death to include the promotion and accumulation of proinflammatory cells that underlie maladaptive repair.<\/jats:p>","DOI":"10.7554\/elife.68603","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T08:00:30Z","timestamp":1626681630000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.68603","source":"Crossref","is-referenced-by-count":148,"title":["Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-211X","authenticated-orcid":true,"given":"Shintaro","family":"Ide","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2845-8481","authenticated-orcid":true,"given":"Kana","family":"Ide","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A","family":"Strausser","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Abe","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Herbek","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-181X","authenticated-orcid":true,"given":"Lori L","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-0561","authenticated-orcid":true,"given":"Steven D","family":"Crowley","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Barisoni","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States"},{"name":"Department of Pathology, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Tata","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4837-0337","authenticated-orcid":true,"given":"Purushothama Rao","family":"Tata","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Duke University School of Medicine, Durham, United States"},{"name":"Regeneration Next, Duke University, Durham, United States"},{"name":"Duke Cancer Institute, Duke University School of Medicine, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3285-8613","authenticated-orcid":true,"given":"Tomokazu","family":"Souma","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, United States"},{"name":"Regeneration Next, Duke University, Durham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"3625","DOI":"10.1242\/dev.151142","article-title":"Psychrophilic proteases dramatically reduce single-cell RNA-seq artifacts: a molecular atlas of kidney development","volume":"144","author":"Adam","year":"2017","journal-title":"Development"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.cell.2019.03.032","article-title":"Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke","volume":"177","author":"Alim","year":"2019","journal-title":"Cell"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1093\/bioinformatics\/btn615","article-title":"AmiGO: online access to ontology and annotation data","volume":"25","author":"AmiGO Hub","year":"2009","journal-title":"Bioinformatics"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1073\/pnas.1316177111","article-title":"Origin of regenerating tubular cells after acute kidney injury","volume":"111","author":"Berger","year":"2014","journal-title":"PNAS"},{"key":"bib5","article-title":"EnhancedVolcano: Publication-ready volcano plots with enhanced colouring and labeling","volume-title":"R Package Version 1.10.0","author":"Blighe","year":"2021","unstructured":"Blighe K, Rana S, Lewis M. 2021. EnhancedVolcano: Publication-ready volcano plots with enhanced colouring and labeling. R Package Version 1.10.0. https:\/\/github.com\/kevinblighe\/EnhancedVolcano."},{"key":"bib6","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","article-title":"NicheNet: modeling intercellular communication by linking ligands to target genes","volume":"17","author":"Browaeys","year":"2020","journal-title":"Nature Methods"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav4754","article-title":"Cyclin G1 and TASCC regulate kidney epithelial cell G2-M arrest and fibrotic maladaptive repair","volume":"11","author":"Canaud","year":"2019","journal-title":"Science Translational Medicine"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","article-title":"The single-cell transcriptional landscape of mammalian organogenesis","volume":"566","author":"Cao","year":"2019","journal-title":"Nature"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1038\/ki.2011.42","article-title":"The severity of acute kidney injury predicts progression to chronic kidney disease","volume":"79","author":"Chawla","year":"2011","journal-title":"Kidney International"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1056\/NEJMra1214243","article-title":"Acute kidney injury and chronic kidney disease as interconnected syndromes","volume":"371","author":"Chawla","year":"2014","journal-title":"New England Journal of Medicine"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1242\/dev.125.5.803","article-title":"Differential expression and function of cadherin-6 during renal epithelium development","volume":"125","author":"Cho","year":"1998","journal-title":"Development"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.stem.2020.06.020","article-title":"Inflammatory signals induce AT2 Cell-Derived Damage-Associated transient progenitors that mediate alveolar regeneration","volume":"27","author":"Choi","year":"2020","journal-title":"Cell Stem Cell"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123151","article-title":"Transcriptional trajectories of human kidney injury progression","volume":"3","author":"Cipp\u00e0","year":"2018","journal-title":"JCI Insight"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0615-0","article-title":"Single-cell analysis reveals congruence between kidney organoids and human fetal kidney","volume":"11","author":"Combes","year":"2019","journal-title":"Genome Medicine"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1242\/dev.182162","article-title":"Single cell analysis of the developing mouse kidney provides deeper insight into marker gene expression and ligand-receptor crosstalk","volume":"146","author":"Combes","year":"2019","journal-title":"Development"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.cell.2017.03.011","article-title":"RIPK3 restricts viral pathogenesis via cell Death-Independent neuroinflammation","volume":"169","author":"Daniels","year":"2017","journal-title":"Cell"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1124\/jpet.111.180984","article-title":"Physiological and molecular characterization of aristolochic acid transport by the kidney","volume":"338","author":"Dickman","year":"2011","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition","volume":"13","author":"Doll","year":"2017","journal-title":"Nature Chemical Biology"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1681\/ASN.2011090887","article-title":"Molecular phenotypes of acute kidney injury in kidney transplants","volume":"23","author":"Famulski","year":"2012","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/nrneph.2015.3","article-title":"Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD","volume":"11","author":"Ferenbach","year":"2015","journal-title":"Nature Reviews Nephrology"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"Friedmann Angeli","year":"2014","journal-title":"Nature Cell Biology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"F1098","DOI":"10.1152\/ajprenal.00199.2018","article-title":"Rodent models of AKI-CKD transition","volume":"315","author":"Fu","year":"2018","journal-title":"American Journal of Physiology-Renal Physiology"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/ng.722","article-title":"Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine","volume":"43","author":"Furuyama","year":"2011","journal-title":"Nature Genetics"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.matbio.2018.02.006","article-title":"Renal fibrosis: primacy of the proximal tubule","volume":"68-69","author":"Gewin","year":"2018","journal-title":"Matrix Biology"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","volume":"20","author":"Hafemeister","year":"2019","journal-title":"Genome Biology"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1093\/ndt\/12.6.1122","article-title":"Expression of cell adhesion molecules in primary renal disease and renal allograft rejection","volume":"12","author":"Hauser","year":"1997","journal-title":"Nephrology Dialysis Transplantation"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"2892","DOI":"10.1001\/jama.293.23.2892","article-title":"Apolipoprotein E and progression of chronic kidney disease","volume":"293","author":"Hsu","year":"2005","journal-title":"Jama"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1146\/annurev-physiol-022516-034227","article-title":"Mechanisms of renal fibrosis","volume":"80","author":"Humphreys","year":"2018","journal-title":"Annual Review of Physiology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1172\/JCI34487","article-title":"Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells","volume":"118","author":"Ichimura","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51756","article-title":"Yolk-sac-derived macrophages progressively expand in the mouse kidney with age","volume":"9","author":"Ide","year":"2020","journal-title":"eLife"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1101\/gad.233247.113","article-title":"SOX9: a stem cell transcriptional regulator of secreted niche signaling factors","volume":"28","author":"Kadaja","year":"2014","journal-title":"Genes & Development"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","volume":"13","author":"Kagan","year":"2017","journal-title":"Nature Chemical Biology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.celrep.2015.12.071","article-title":"Sox9-Positive progenitor cells play a key role in renal tubule epithelial regeneration in mice","volume":"14","author":"Kang","year":"2016","journal-title":"Cell Reports"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1097\/CCM.0000000000003555","article-title":"Ferroptosis contributes to neuronal death and functional outcome after traumatic brain injury","volume":"47","author":"Kenny","year":"2019","journal-title":"Critical Care Medicine"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"15874","DOI":"10.1073\/pnas.2005477117","article-title":"Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury","volume":"117","author":"Kirita","year":"2020","journal-title":"PNAS"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"4797","DOI":"10.1172\/JCI122313","article-title":"Proximal tubule ATR regulates DNA repair to prevent maladaptive renal injury responses","volume":"129","author":"Kishi","year":"2019","journal-title":"Journal of Clinical Investigation"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/s41556-020-0542-8","article-title":"Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis","volume":"22","author":"Kobayashi","year":"2020","journal-title":"Nature Cell Biology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1016\/j.celrep.2015.07.034","article-title":"Sox9 activation highlights a cellular pathway of renal repair in the acutely injured mammalian kidney","volume":"12","author":"Kumar","year":"2015","journal-title":"Cell Reports"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1073\/pnas.1310653110","article-title":"Differentiated kidney epithelial cells repair injured proximal tubule","volume":"111","author":"Kusaba","year":"2014","journal-title":"PNAS"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41586-018-0414-6","article-title":"RNA velocity of single cells","volume":"560","author":"La Manno","year":"2018","journal-title":"Nature"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1681\/ASN.2014010028","article-title":"Functional genomic annotation of genetic risk loci highlights inflammation and epithelial biology networks in CKD","volume":"26","author":"Ledo","year":"2015","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/s42255-020-0238-1","article-title":"Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality","volume":"2","author":"Legouis","year":"2020","journal-title":"Nature Metabolism"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/ki.2013.153","article-title":"Raising awareness of acute kidney injury: a global perspective of a silent killer","volume":"84","author":"Lewington","year":"2013","journal-title":"Kidney International"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1038\/s41418-019-0299-4","article-title":"Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia\/reperfusion","volume":"26","author":"Li","year":"2019","journal-title":"Cell Death & Differentiation"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"16836","DOI":"10.1073\/pnas.1415518111","article-title":"Synchronized renal tubular cell death involves ferroptosis","volume":"111","author":"Linkermann","year":"2014","journal-title":"PNAS"},{"key":"bib48","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94716","article-title":"Molecular characterization of the transition from acute to chronic kidney injury following ischemia\/reperfusion","volume":"2","author":"Liu","year":"2017","journal-title":"JCI Insight"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1016\/j.cell.2015.05.002","article-title":"Highly parallel Genome-wide expression profiling of individual cells using nanoliter droplets","volume":"161","author":"Macosko","year":"2015","journal-title":"Cell"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nn.2467","article-title":"A robust and high-throughput cre reporting and characterization system for the whole mouse brain","volume":"13","author":"Madisen","year":"2010","journal-title":"Nature Neuroscience"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1006\/dbio.2000.9738","article-title":"Kidney development in cadherin-6 mutants: delayed mesenchyme-to-epithelial conversion and loss of nephrons","volume":"223","author":"Mah","year":"2000","journal-title":"Developmental Biology"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1681\/ASN.2020030326","article-title":"Harnessing expressed single nucleotide variation and single cell RNA sequencing to define immune cell chimerism in the rejecting kidney transplant","volume":"31","author":"Malone","year":"2020","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib53","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.97497","article-title":"Hnf4a deletion in the mouse kidney phenocopies fanconi renotubular syndrome","volume":"3","author":"Marable","year":"2018","journal-title":"JCI Insight"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.1681\/ASN.2020020184","article-title":"Hnf4a is required for the development of Cdh6-Expressing progenitors into proximal tubules in the mouse kidney","volume":"31","author":"Marable","year":"2020","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.immuni.2014.09.016","article-title":"The necroptosis adaptor RIPK3 promotes injury-induced cytokine expression and tissue repair","volume":"41","author":"Moriwaki","year":"2014","journal-title":"Immunity"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1007\/s00018-016-2203-4","article-title":"Necroptosis-independent signaling by the RIP kinases in inflammation","volume":"73","author":"Moriwaki","year":"2016","journal-title":"Cellular and Molecular Life Sciences"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"3631","DOI":"10.1007\/s00018-017-2547-4","article-title":"Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure","volume":"74","author":"M\u00fcller","year":"2017","journal-title":"Cellular and Molecular Life Sciences"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.kint.2016.08.023","article-title":"Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression","volume":"91","author":"Nezu","year":"2017","journal-title":"Kidney International"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nm.2290","article-title":"The ngal reporter mouse detects the response of the kidney to injury in real time","volume":"17","author":"Paragas","year":"2011","journal-title":"Nature Medicine"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1126\/science.aar2131","article-title":"Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease","volume":"360","author":"Park","year":"2018","journal-title":"Science"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.devcel.2019.10.005","article-title":"Single-Cell profiling reveals sex, lineage, and regional diversity in the mouse kidney","volume":"51","author":"Ransick","year":"2019","journal-title":"Developmental Cell"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1093\/hmg\/ddq558","article-title":"SOX9 controls epithelial branching by activating RET effector genes during kidney development","volume":"20","author":"Reginensi","year":"2011","journal-title":"Human Molecular Genetics"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.kint.2019.07.016","article-title":"The transcription factor Twist1 in the distal nephron but not in macrophages propagates aristolochic acid nephropathy","volume":"97","author":"Ren","year":"2020","journal-title":"Kidney International"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1053\/j.gastro.2015.07.004","article-title":"SOX9 maintains reserve stem cells and preserves radioresistance in mouse small intestine","volume":"149","author":"Roche","year":"2015","journal-title":"Gastroenterology"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1681\/ASN.2020010052","article-title":"Single-Cell profiling of AKI in a murine model reveals novel transcriptional signatures, profibrotic phenotype, and Epithelial-to-Stromal crosstalk","volume":"31","author":"Rudman-Melnick","year":"2020","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1126\/science.aat5031","article-title":"Spatiotemporal immune zonation of the human kidney","volume":"365","author":"Stewart","year":"2019","journal-title":"Science"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1097\/MNH.0000000000000424","article-title":"Acute kidney injury to chronic kidney disease transition: insufficient cellular stress response","volume":"27","author":"Strausser","year":"2018","journal-title":"Current Opinion in Nephrology and Hypertension"},{"key":"bib69","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17358-3","article-title":"Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis","volume":"11","author":"Strunz","year":"2020","journal-title":"Nature Communications"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of Single-Cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.stem.2018.03.018","article-title":"Myoepithelial cells of submucosal glands can function as reserve stem cells to regenerate airways after injury","volume":"22","author":"Tata","year":"2018","journal-title":"Cell Stem Cell"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.ccr.2013.04.020","article-title":"Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming","volume":"23","author":"Tiwari","year":"2013","journal-title":"Cancer Cell"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nature Biotechnology"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.cell.2017.09.044","article-title":"PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals","volume":"171","author":"Wenzel","year":"2017","journal-title":"Cell"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"19619","DOI":"10.1073\/pnas.1908706116","article-title":"The single-cell transcriptomic landscape of early human diabetic nephropathy","volume":"116","author":"Wilson","year":"2019","journal-title":"PNAS"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1172\/JCI117214","article-title":"Localization of proliferating cell nuclear antigen, Vimentin, c-Fos, and clusterin in the postischemic kidney\u00a0evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells","volume":"93","author":"Witzgall","year":"1994","journal-title":"Journal of Clinical Investigation"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic Cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1016\/j.freeradbiomed.2012.02.043","article-title":"Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain","volume":"52","author":"Yoo","year":"2012","journal-title":"Free Radical Biology and Medicine"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1016\/j.bbrc.2016.08.124","article-title":"Identification of ACSL4 as a biomarker and contributor of ferroptosis","volume":"478","author":"Yuan","year":"2016","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib80","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02871-6","article-title":"XJB-5-131 inhibited ferroptosis in tubular epithelial cells after ischemia-reperfusion injury","volume":"11","author":"Zhao","year":"2020","journal-title":"Cell Death & Disease"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/68603\/elife-68603-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/68603\/elife-68603-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/68603","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:16:20Z","timestamp":1697058980000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/68603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,19]]},"references-count":80,"alternative-id":["10.7554\/eLife.68603"],"URL":"https:\/\/doi.org\/10.7554\/elife.68603","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.03.23.436661","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2021.03.23.436661","asserted-by":"object"}],"references":[{"id-type":"accession","id":"GSE94333","asserted-by":"subject"},{"id-type":"accession","id":"GSE131882","asserted-by":"subject"},{"id-type":"accession","id":"GSE145927","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE161201","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.68603.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.68603.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,19]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e68603"}}