en-usIn this collection, JASN Editors are pleased to present a series of papers on the application of single cell methods to study kidney disease. Included in this series are reviews addressing the challenges and innovative studies using these techniques to define a comprehensive cellular anatomy of the kidney in health and disease. The papers illustrate the methods applied both to biopsies from patients and to samples from animal studies.<p></p>Fri, 26 Apr 2024 11:04:55 GMThttp://cct.highwire.org/feeds/asn/single-cell-sequencing.rssBackground Nephron endowment is a key determinant of hypertension and kidney disease in later life. Epigenetic changes have been proposed to mediate fetal programming and nephron number. DNA cytosine methylation, which plays a critical role in gene regulation, is affected by proteins encoded by the 10-11 translocation (TET) DNA demethylase gene family (Tet1, Tet2, and Tet3), but the roles of TET proteins in kidney development and nephron endowment have not been characterized. Methods To study whether epigenetic changes—specifically, active DNA hydroxymethylation mediated by Tet1, Tet2, and Tet3—are necessary for nephron progenitor differentiation and nephron endowment, we generated mice with deletion of Tet1, Tet2, or Tet3 in Six2-positive nephron progenitors cells (NPCs). We then performed unbiased omics profiling, including whole-genome bisulfite sequencing on isolated Six2-positive NPCs and single-cell RNA sequencing on kidneys from newborn mice. Results We did not observe changes in kidney development or function in mice with NPCspecific deletion of Tet1, Tet2, Tet3 or Tet1/Tet2 or Tet1/Tet3. On the other hand, mice with combined Tet2 and Tet3 loss in Six2-positive NPCs failed to form nephrons, leading to kidney failure and perinatal death. Tet2 and Tet3 loss in Six2-positive NPCs resulted in defective mesenchymal to epithelial transition and renal vesicle differentiation. Whole-genome bisulfite sequencing, single-cell RNA sequencing, and gene and protein expression analysis identified a defect in expression in multiple genes, including the WNT-β-catenin signaling pathway, due to a failure in demethylation of these loci in the absence of Tet2 and Tet3. Conclusions These findings suggest that Tet2- and Tet3-mediated active cytosine hydroxymethylation in NPCs play a key role in kidney development and nephron endowment.xiujie.liang@pennmedicine.upenn.edu10.1681/ASN.2022040460Thu, 15 Dec 2022 11:34:35 GMT-08:00Tet2- and Tet3-Mediated Cytosine Hydroxymethylation in Six2 Progenitor Cells in Mice Is Critical for Nephron Progenitor Differentiation and Nephron EndowmentBackground Nephron endowment is a key determinant of hypertension and kidney disease in later life. Epigenetic changes have been proposed to mediate fetal programming and nephron number. DNA cytosine methylation, which plays a critical role in gene regulation, is affected by proteins encoded by the 10-11 translocation (TET) DNA demethylase gene family (Tet1, Tet2, and Tet3), but the roles of TET proteins in kidney development and nephron endowment have not been characterized. Methods To study whether epigenetic changes—specifically, active DNA hydroxymethylation mediated by Tet1, Tet2, and Tet3—are necessary for nephron progenitor differentiation and nephron endowment, we generated mice with deletion of Tet1, Tet2, or Tet3 in Six2-positive nephron progenitors cells (NPCs). We then performed unbiased omics profiling, including whole-genome bisulfite sequencing on isolated Six2-positive NPCs and single-cell RNA sequencing on kidneys from newborn mice. Results We did not observe changes in kidney development or function in mice with NPCspecific deletion of Tet1, Tet2, Tet3 or Tet1/Tet2 or Tet1/Tet3. On the other hand, mice with combined Tet2 and Tet3 loss in Six2-positive NPCs failed to form nephrons, leading to kidney failure and perinatal death. Tet2 and Tet3 loss in Six2-positive NPCs resulted in defective mesenchymal to epithelial transition and renal vesicle differentiation. Whole-genome bisulfite sequencing, single-cell RNA sequencing, and gene and protein expression analysis identified a defect in expression in multiple genes, including the WNT-β-catenin signaling pathway, due to a failure in demethylation of these loci in the absence of Tet2 and Tet3. Conclusions These findings suggest that Tet2- and Tet3-mediated active cytosine hydroxymethylation in NPCs play a key role in kidney development and nephron endowment.Liang, XiujieAranyi, TamasZhou, JianfuGuan, YutingHu, HailongLiu, HongboSusztak, Katalin2022-12-15T11:34:35-08:00doi:10.1681/ASN.2022040460hwp:resource-id:jnephrol;ASN.2022040460v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Basic ResearchOriginal Article - Basic Researchresearch-article202210.1681/ASN.20220404601046-66731533-34502022-12-15T11:34:35-08:00Journal of the American Society of NephrologyOriginal Article - Basic ResearchASN.202204046010.1681/ASN.2021111518Mon, 17 Oct 2022 07:25:15 GMT-07:00Anatomical Evidence for Parasympathetic Innervation of the Renal Vasculature and PelvisCheng, XiaofengZhang, YongshengChen, RuixiQian, ShenghuiLv, HaijunLiu, XiuliZeng, Shaoqun2022-10-17T07:25:15-07:00doi:10.1681/ASN.2021111518hwp:resource-id:jnephrol;33/12/2194American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney anatomy, arteries, acetylcholine, gene transcriptionBasic ResearchNormal Kidney Structure and FunctionBasic ResearchNormal Kidney Structure and Functionresearch-article20222022-12-01December 202210.1681/ASN.20211115181046-66731533-34502022-10-17T07:25:15-07:002022-12Journal of the American Society of NephrologyBasic Research3312122194i2210i10.1681/ASN.2022050601Tue, 02 Aug 2022 12:56:00 GMT-07:00Early Molecular Events Mediating Loss of Aquaporin-2 during Ureteral Obstruction in RatsSung, Chih-ChienPoll, Brian G.Lin, Shih-HuaMurillo-de-Ozores, Adrian R.Chou, Chung-LinChen, LiheYang, Chin-RangChen, Min-HsiuHsu, Yu-JueiKnepper, Mark A.2022-08-02T12:56:00-07:00doi:10.1681/ASN.2022050601hwp:resource-id:jnephrol;33/11/2040American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyaquaporin-2, P-body, collecting ducts, ureteral obstruction, RNA-Seq, lipopolysaccharideBasic ResearchSystems BiologyBasic ResearchSystems Biologyresearch-article20222022-11-01November 202210.1681/ASN.20220506011046-66731533-34502022-08-02T12:56:00-07:002022-11Journal of the American Society of NephrologyBasic Research3311112040i2058i10.1681/ASN.2021091213Tue, 05 Apr 2022 12:39:29 GMT-07:00Single-Cell Chromatin and Gene-Regulatory Dynamics of Mouse Nephron ProgenitorsHilliard, SylviaTortelote, GiovaneLiu, HongbingChen, Chao-HuiEl-Dahr, Samir S.2022-04-05T12:39:29-07:00doi:10.1681/ASN.2021091213hwp:resource-id:jnephrol;33/7/1308American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologygenetics and development, kidney development, renal development, renal stem cell, single-cell, epigenetic, mice, chromatin, nephrons, regulator genesBasic ResearchDevelopment of the KidneyBasic ResearchDevelopment of the Kidneyresearch-article20222022-07-01July 202210.1681/ASN.20210912131046-66731533-34502022-04-05T12:39:29-07:002022-07Journal of the American Society of NephrologyBasic Research3371308132210.1681/ASN.2021121548Mon, 16 May 2022 01:17:09 GMT-07:00Arginase-1 Is Required for Macrophage-Mediated Renal Tubule RegenerationShin, Naomi S.Marlier, ArnaudXu, LeyuanDoilicho, NatnaelLinberg, DanielGuo, JiankanCantley, Lloyd G.2022-05-16T13:17:09-07:00doi:10.1681/ASN.2021121548hwp:resource-id:jnephrol;33/6/1077American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney repair, macrophage, arginase-1, kidney tubules, regenerationRapid CommunicationAcute Kidney InjuryRapid CommunicationAcute Kidney Injuryresearch-article20222022-06-01June 202210.1681/ASN.20211215481046-66731533-34502022-05-16T13:17:09-07:002022-06Journal of the American Society of NephrologyRapid Communication3366611111077i1051212321241086i10532124212510.1681/ASN.2021060784Wed, 27 Apr 2022 08:25:13 GMT-07:00Molecular Characterization of Membranous NephropathySealfon, RachelMariani, LauraAvila-Casado, CarmenNair, VijiMenon, RajasreeFunk, JulienWong, AaronLerner, GabrielHayashi, NorifumiTroyanskaya, OlgaKretzler, MatthiasBeck, Laurence H.2022-04-27T08:25:13-07:00doi:10.1681/ASN.2021060784hwp:resource-id:jnephrol;33/6/1208American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, transcriptional profiling, podocyte, single-cell sequencing, machine learning, scRNA-seq, machine learningClinical ResearchGlomerulonephritis and Interstitial NephritisClinical ResearchGlomerulonephritis and Interstitial Nephritisresearch-article20222022-06-01June 202210.1681/ASN.20210607841046-66731533-34502022-04-27T08:25:13-07:002022-06Journal of the American Society of NephrologyClinical Research336612121208105723212322122110592322232310.1681/ASN.2021030278Wed, 02 Feb 2022 09:35:54 GMT-08:00A Comprehensive Immune Cell Atlas of Cystic Kidney Disease Reveals the Involvement of Adaptive Immune Cells in Injury-Mediated Cyst Progression in MiceSong, Cheng J.Li, ZhangAhmed, Ummey Khalecha BinthaBland, Sarah J.Yashchenko, AlexLiu, ShanrunAloria, Ernald J.Lever, Jeremie M.Gonzalez, Nancy M.Bickel, Marisa A.Giles, Cory B.Georgescu, ConstantinWren, Jonathan D.Lang, Mark L.Benveniste, Etty N.Harrington, Laurie E.Tsiokas, LeoGeorge, James F.Jones, Kenneth L.Crossman, David K.Agarwal, AnupamMrug, MichalYoder, Bradley K.Hopp, KatharinaZimmerman, Kurt A.2022-02-02T09:35:54-08:00doi:10.1681/ASN.2021030278hwp:resource-id:jnephrol;33/4/747American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycystic kidney, immunology, ischemia-reperfusionBasic ResearchBasic Researchresearch-article20222022-04-01April 202210.1681/ASN.20210302781046-66731533-34502022-02-02T09:35:54-08:002022-04Journal of the American Society of NephrologyBasic Research33474776810.1681/ASN.2021070881Tue, 04 Jan 2022 09:36:13 GMT-08:00Vitamin C Deficiency Causes Cell Type–Specific Epigenetic Reprogramming and Acute Tubular Necrosis in a Mouse ModelYu, ZihuiXu, ZiyingLiang, YuanYin, PengbinShi, YueYu, JiayiHao, JunfengWang, TingCi, Weimin2022-01-04T09:36:13-08:00doi:10.1681/ASN.2021070881hwp:resource-id:jnephrol;33/3/531American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyvitamin C, DNA methylation, N6-methyladenosine, acute tubular necrosis, renal homeostasis, single-cell RNA sequencing, ascorbic acid deficiency, epigenomicsBasic ResearchBasic Researchresearch-article20222022-03-01March 202210.1681/ASN.20210708811046-66731533-34502022-01-04T09:36:13-08:002022-03Journal of the American Society of NephrologyBasic Research33353154610.1681/ASN.2021040439Fri, 17 Dec 2021 11:42:38 GMT-08:00Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and InflammationGuo, XiaojiaXu, LeyuanVelazquez, HeinoChen, Tian-MinWilliams, Ryan M.Heller, Daniel A.Burtness, BarbaraSafirstein, RobertDesir, Gary V.2021-12-17T11:42:38-08:00doi:10.1681/ASN.2021040439hwp:resource-id:jnephrol;33/2/342American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin, cisplatin nephrotoxicity, chronic renal disease, cytokines, macrophages, mitochondria, oxidative stress, proximal tubule, renal protection, cell deathBasic ResearchBasic Researchresearch-article20222022-02-01February 202210.1681/ASN.20210404391046-66731533-34502021-12-17T11:42:38-08:002022-02Journal of the American Society of NephrologyBasic Research332234225535625610.1681/ASN.2021081150Wed, 01 Dec 2021 09:28:12 GMT-08:00Spatially Resolved Transcriptomic Analysis of Acute Kidney Injury in a Female Murine ModelDixon, Eryn E.Wu, HaojiaMuto, YoshiharuWilson, Parker C.Humphreys, Benjamin D.2021-12-01T09:28:12-08:00doi:10.1681/ASN.2021081150hwp:resource-id:jnephrol;33/2/279American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologytranscriptomics, AKI, spatialRapid CommunicationsRapid Communicationsresearch-article20222022-02-01February 202210.1681/ASN.20210811501046-66731533-34502021-12-01T09:28:12-08:002022-02Journal of the American Society of NephrologyRapid Communications332279289Fifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.10.1681/ASN.2021081073Wed, 17 Nov 2021 10:26:37 GMT-08:00Regrow or Repair: An Update on Potential Regenerative Therapies for the KidneyFifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.Little, Melissa H.Humphreys, Benjamin D.2021-11-17T10:26:37-08:00doi:10.1681/ASN.2021081073hwp:resource-id:jnephrol;33/1/15American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, stem cell, regenerative therapies, single-cell expression profiling, pluripotent stem cell, directed differentiation, tissue repair, gene editingReviewReviewreview-article20222022-01-01January 202210.1681/ASN.20210810731046-66731533-34502021-11-17T10:26:37-08:002022-01Journal of the American Society of NephrologyReview331153210.1681/ASN.2021030426Tue, 30 Nov 2021 06:14:42 GMT-08:00IL-17 Receptor C Signaling Controls CD4+ TH17 Immune Responses and Tissue Injury in Immune-Mediated Kidney DiseasesSchmidt, TilmanLuebbe, JonasKilian, ChristophRiedel, Jan-HendrikHiekmann, SonjaAsada, NariakiGinsberg, PaulineRobben, LennartSong, NingKaffke, AnnaPeters, AnettBorchers, AlinaFlavell, Richard A.Gagliani, NicolaPelzcar, PenelopeHuber, SamuelHuber, Tobias B.Turner, Jan-EricPaust, Hans-JoachimKrebs, Christian F.Panzer, Ulf2021-11-30T06:14:42-08:00doi:10.1681/ASN.2021030426hwp:resource-id:jnephrol;32/12/3081American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycytokines, glomerulonephritis, immunology, lymphocytesBasic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210304261046-66731533-34502021-11-30T06:14:42-08:002021-12Journal of the American Society of NephrologyBasic Research32123081309810.1681/ASN.2020081143Mon, 21 Jun 2021 09:55:14 GMT-07:00Single-Nucleus RNA Sequencing Identifies New Classes of Proximal Tubular Epithelial Cells in Kidney FibrosisLu, Yueh-AnLiao, Chia-TeRaybould, RachelTalabani, BnarGrigorieva, IrinaSzomolay, BarbaraBowen, TimothyAndrews, RobertTaylor, Philip R.Fraser, Donald2021-06-21T09:55:14-07:00doi:10.1681/ASN.2020081143hwp:resource-id:jnephrol;32/10/2501American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycell biology and structure, chronic kidney disease, epithelial, kidney tubule, mRNA, proximal tubule, renal epithelial cell, renal fibrosis, renal tubular epithelial cells, scRNA-seqBasic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20200811431046-66731533-34502021-06-21T09:55:14-07:002021-10Journal of the American Society of NephrologyBasic Research3210102501i2516iSingle-cell RNA sequencing (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) allow transcriptomic profiling of thousands of cells from a renal biopsy specimen at a single-cell resolution. Both methods are promising tools to unravel the underlying pathophysiology of glomerular diseases. This review provides an overview of the technical challenges that should be addressed when designing single-cell transcriptomics experiments that focus on glomerulopathies. The isolation of glomerular cells from core needle biopsy specimens for single-cell transcriptomics remains difficult and depends upon five major factors. First, core needle biopsies generate little tissue material, and several samples are required to identify glomerular cells. Second, both fresh and frozen tissue samples may yield glomerular cells, although every experimental pipeline has different (dis)advantages. Third, enrichment for glomerular cells in human tissue before single-cell analysis is challenging because no effective standardized pipelines are available. Fourth, the current warm cell-dissociation protocols may damage glomerular cells and induce transcriptional artifacts, which can be minimized by using cold dissociation techniques at the cost of less efficient cell dissociation. Finally, snRNA-seq methods may be superior to scRNA-seq in isolating glomerular cells; however, the efficacy of snRNA-seq on core needle biopsy specimens remains to be proven. The field of single-cell omics is rapidly evolving, and the integration of these techniques in multiomics assays will undoubtedly create new insights in the complex pathophysiology of glomerular diseases.ben.sprangers@uzleuven.be10.1681/ASN.2021020157Thu, 17 Jun 2021 07:41:25 GMT-07:00Current Methodological Challenges of Single-Cell and Single-Nucleus RNA-Sequencing in Glomerular DiseasesSingle-cell RNA sequencing (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) allow transcriptomic profiling of thousands of cells from a renal biopsy specimen at a single-cell resolution. Both methods are promising tools to unravel the underlying pathophysiology of glomerular diseases. This review provides an overview of the technical challenges that should be addressed when designing single-cell transcriptomics experiments that focus on glomerulopathies. The isolation of glomerular cells from core needle biopsy specimens for single-cell transcriptomics remains difficult and depends upon five major factors. First, core needle biopsies generate little tissue material, and several samples are required to identify glomerular cells. Second, both fresh and frozen tissue samples may yield glomerular cells, although every experimental pipeline has different (dis)advantages. Third, enrichment for glomerular cells in human tissue before single-cell analysis is challenging because no effective standardized pipelines are available. Fourth, the current warm cell-dissociation protocols may damage glomerular cells and induce transcriptional artifacts, which can be minimized by using cold dissociation techniques at the cost of less efficient cell dissociation. Finally, snRNA-seq methods may be superior to scRNA-seq in isolating glomerular cells; however, the efficacy of snRNA-seq on core needle biopsy specimens remains to be proven. The field of single-cell omics is rapidly evolving, and the integration of these techniques in multiomics assays will undoubtedly create new insights in the complex pathophysiology of glomerular diseases.Deleersnijder, DriesCallemeyn, JasperArijs, IngridNaesens, MaartenVan Craenenbroeck, Amaryllis H.Lambrechts, DietherSprangers, Ben2021-06-17T07:41:25-07:00doi:10.1681/ASN.2021020157hwp:resource-id:jnephrol;32/8/1838American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, transcriptional profiling, molecular biology, renal cell biologyReviewsReviewsreview-article20212021-08-01August 202110.1681/ASN.20210201571046-66731533-34502021-06-17T07:41:25-07:002021-08Journal of the American Society of NephrologyReviews32818381852Over the last 5 years, single cell methods have enabled the monitoring of gene and protein expression, genetic, and epigenetic changes in thousands of individual cells in a single experiment. With the improved measurement and the decreasing cost of the reactions and sequencing, the size of these datasets is increasing rapidly. The critical bottleneck remains the analysis of the wealth of information generated by single cell experiments. In this review, we give a simplified overview of the analysis pipelines, as they are typically used in the field today. We aim to enable researchers starting out in single cell analysis to gain an overview of challenges and the most commonly used analytical tools. In addition, we hope to empower others to gain an understanding of how typical readouts from single cell datasets are presented in the published literature.10.1681/ASN.2020121742Mon, 15 Mar 2021 11:23:41 GMT-07:00How to Get Started with Single Cell RNA Sequencing Data AnalysisOver the last 5 years, single cell methods have enabled the monitoring of gene and protein expression, genetic, and epigenetic changes in thousands of individual cells in a single experiment. With the improved measurement and the decreasing cost of the reactions and sequencing, the size of these datasets is increasing rapidly. The critical bottleneck remains the analysis of the wealth of information generated by single cell experiments. In this review, we give a simplified overview of the analysis pipelines, as they are typically used in the field today. We aim to enable researchers starting out in single cell analysis to gain an overview of challenges and the most commonly used analytical tools. In addition, we hope to empower others to gain an understanding of how typical readouts from single cell datasets are presented in the published literature.Balzer, Michael S.Ma, ZiyuanZhou, JianfuAbedini, AminSusztak, Katalin2021-03-15T11:23:41-07:00doi:10.1681/ASN.2020121742hwp:resource-id:jnephrol;32/6/1279American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysingle cell RNA-sequencing, transcriptomics, kidney, analysisReviewsReviewsreview-article20212021-06-01June 202110.1681/ASN.20201217421046-66731533-34502021-03-15T11:23:41-07:002021-06Journal of the American Society of NephrologyReviews3261279129210.1681/ASN.2020101407Thu, 04 Mar 2021 09:32:57 GMT-08:00Targeted Single-Cell RNA-seq Identifies Minority Cell Types of Kidney Distal NephronChen, LiheChou, Chun-LinKnepper, Mark A.2021-03-04T09:32:57-08:00doi:10.1681/ASN.2020101407hwp:resource-id:jnephrol;32/4/886American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyscRNA-seq, distal convoluted tubule, thick ascending limb, macula densaBasic ResearchBasic Researchresearch-article20212021-04-01April 202110.1681/ASN.20201014071046-66731533-34502021-03-04T09:32:57-08:002021-04Journal of the American Society of NephrologyBasic Research3244488676889789677191210.1681/ASN.2020070930Wed, 25 Nov 2020 01:16:05 GMT-08:00Kidney Single-cell Transcriptomes Predict Spatial Corticomedullary Gene Expression and Tissue Osmolality GradientsHinze, ChristianKaraiskos, NikosBoltengagen, AnastasiyaWalentin, KatharinaRedo, KleaHimmerkus, NinaBleich, MarkusPotter, S. StevenPotter, Andrew S.Eckardt, Kai-UweKocks, ChristineRajewsky, NikolausSchmidt-Ott, Kai M.2020-11-25T13:16:05-08:00doi:10.1681/ASN.2020070930hwp:resource-id:jnephrol;32/2/291American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologymicroenvironment, spatial resolution single-cell transcriptomics, osmolality gradient, osmogenes, cell typesBasic ResearchBasic Researchresearch-article20212021-02-01February 202110.1681/ASN.20200709301046-66731533-34502020-11-25T13:16:05-08:002021-02Journal of the American Society of NephrologyBasic Research32229130610.1681/ASN.2020010052Wed, 28 Oct 2020 07:18:33 GMT-07:00Single-Cell Profiling of AKI in a Murine Model Reveals Novel Transcriptional Signatures, Profibrotic Phenotype, and Epithelial-to-Stromal CrosstalkRudman-Melnick, ValeriaAdam, MikePotter, AndrewChokshi, Saagar M.Ma, QingDrake, Keri A.Schuh, Meredith P.Kofron, J. MatthewDevarajan, PrasadPotter, S. Steven2020-10-28T07:18:33-07:00doi:10.1681/ASN.2020010052hwp:resource-id:jnephrol;31/12/2793American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, single-cell, renal developmental genes, cellular crosstalkBasic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20200100521046-66731533-34502020-10-28T07:18:33-07:002020-12Journal of the American Society of NephrologyBasic Research31122793281410.1681/ASN.2020060806Fri, 25 Sep 2020 05:42:23 GMT-07:00Kidney Single-Cell Atlas Reveals Myeloid Heterogeneity in Progression and Regression of Kidney DiseaseConway, Bryan R.O’Sullivan, Eoin D.Cairns, CarolynnO’Sullivan, JamesSimpson, Daniel J.Salzano, AngelaConnor, KatieDing, PengHumphries, DuncanStewart, KevinTeenan, OliverPius, RiinuHenderson, Neil C.Bénézech, CécileRamachandran, PrakashFerenbach, DavidHughes, JeremyChandra, TamirDenby, Laura2020-09-25T05:42:23-07:00doi:10.1681/ASN.2020060806hwp:resource-id:jnephrol;31/12/2833American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, kidney disease, scRNA sequencing, myeloid cellsBasic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20200608061046-66731533-34502020-09-25T05:42:23-07:002020-12Journal of the American Society of NephrologyBasic Research31122833285410.1681/ASN.2020020220Fri, 10 Jul 2020 10:44:14 GMT-07:00Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to InjuryChung, Jun-JaeGoldstein, LeonardChen, Ying-Jiun J.Lee, JiyeonWebster, Joshua D.Roose-Girma, MeronePaudyal, Sharad C.Modrusan, ZoraDey, AnweshaShaw, Andrey S.2020-07-10T10:44:14-07:00doi:10.1681/ASN.2020020220hwp:resource-id:jnephrol;31/10/2341American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyanti-GBM disease, chronic kidney disease, diabetic glomerulopathy, glomerular disease, transcriptional profilingBasic ResearchBasic Researchresearch-article20202020-10-01October 202010.1681/ASN.20200202201046-66731533-34502020-07-10T10:44:14-07:002020-10Journal of the American Society of NephrologyBasic Research31102341235410.1681/ASN.2020081180Thu, 03 Sep 2020 12:26:12 GMT-07:00Two Tales of Single-Cell RNA Sequencing: Gene Expression and Alternative Splicing in Mouse Kidney DevelopmentChen, Lihe2020-09-03T12:26:12-07:00doi:10.1681/ASN.2020081180hwp:resource-id:jnephrol;31/10/2234American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, single-cell RNA-seq, alternative splicingEditorialsEditorialseditorial20202020-10-01October 202010.1681/ASN.20200811801046-66731533-34502020-09-03T12:26:12-07:002020-10Journal of the American Society of NephrologyEditorials311010223422782236229110.1681/ASN.2020030326Wed, 15 Jul 2020 12:55:09 GMT-07:00Harnessing Expressed Single Nucleotide Variation and Single Cell RNA Sequencing To Define Immune Cell Chimerism in the Rejecting Kidney TransplantMalone, Andrew F.Wu, HaojiaFronick, CatrinaFulton, RobertGaut, Joseph P.Humphreys, Benjamin D.2020-07-15T12:55:09-07:00doi:10.1681/ASN.2020030326hwp:resource-id:jnephrol;31/9/1977American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologygene expression, transplantation, transcriptional profilingBasic ResearchBasic Researchresearch-article20202020-09-01September 202010.1681/ASN.20200303261046-66731533-34502020-07-15T12:55:09-07:002020-09Journal of the American Society of NephrologyBasic Research3191977198610.1681/ASN.2019080832Mon, 09 Dec 2019 07:20:45 GMT-08:00Single-Cell RNA Sequencing Reveals Renal Endothelium Heterogeneity and Metabolic Adaptation to Water DeprivationDumas, Sébastien J.Meta, EldaBorri, MilaGoveia, JermaineRohlenova, KaterinaConchinha, Nadine V.Falkenberg, KimTeuwen, Laure-Annede Rooij, LauraKalucka, JoannaChen, RongyuanKhan, ShawezTaverna, FedericoLu, WeisiParys, MagdalenaDe Legher, CarlaVinckier, StefanKarakach, Tobias K.Schoonjans, LucLin, LinBolund, LarsDewerchin, MiekeEelen, GuyRabelink, Ton J.Li, XuriLuo, YonglunCarmeliet, Peter2019-12-09T07:20:45-08:00doi:10.1681/ASN.2019080832hwp:resource-id:jnephrol;31/1/118American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal endothelial cells, scRNA-sequencing, heterogeneity, dehydration, urine concentration, oxidative phosphorylationBasic ResearchBasic Researchresearch-article20202020-01-01January 202010.1681/ASN.20190808321046-66731533-34502019-12-09T07:20:45-08:002020-01Journal of the American Society of NephrologyBasic Research31111181138210.1681/ASN.2019040335Wed, 28 Aug 2019 07:31:44 GMT-07:00Single-Cell Transcriptomic Map of the Human and Mouse BladdersYu, ZhenyuanLiao, JinlingChen, YangZou, ChunlinZhang, HaiyingCheng, JiwenLiu, DeyunLi, TianyuZhang, QingyunLi, JiapingYang, XiaoboYe, YuHuang, ZhiguangLong, XinyangYang, RirongMo, Zengnan2019-08-28T07:31:44-07:00doi:10.1681/ASN.2019040335hwp:resource-id:jnephrol;30/11/2159American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologysingle-cell RNA sequencing, single-cell transcriptomic map, bladder cells, interstitial cells, epithelial cellsBasic ResearchBasic Researchresearch-article20192019-11-01November 201910.1681/ASN.20190403351046-66731533-34502019-08-28T07:31:44-07:002019-11Journal of the American Society of NephrologyBasic Research30112159217610.1681/ASN.2018090896Thu, 07 Mar 2019 07:45:22 GMT-08:00Single-Cell RNA Profiling of Glomerular Cells Shows Dynamic Changes in Experimental Diabetic Kidney DiseaseFu, JiaAkat, Kemal M.Sun, ZeguoZhang, WeijiaSchlondorff, DetlefLiu, ZhihongTuschl, ThomasLee, KyungHe, John Cijiang2019-03-07T07:45:22-08:00doi:10.1681/ASN.2018090896hwp:resource-id:jnephrol;30/4/533American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulus, diabetic nephropathy, transcriptional profiling, mesangial cells, glomerular endothelial cells, macrophagesBasic ResearchBasic Researchresearch-article20192019-04-01April 201910.1681/ASN.20180908961046-66731533-34502019-03-07T07:45:22-08:002019-04Journal of the American Society of NephrologyBasic Research30453354510.1681/ASN.2018090912Mon, 03 Dec 2018 07:33:15 GMT-08:00Advantages of Single-Nucleus over Single-Cell RNA Sequencing of Adult Kidney: Rare Cell Types and Novel Cell States Revealed in FibrosisWu, HaojiaKirita, YuheiDonnelly, Erinn L.Humphreys, Benjamin D.2018-12-03T07:33:15-08:00doi:10.1681/ASN.2018090912hwp:resource-id:jnephrol;30/1/23American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyRNA-sequencing, fibrosis, single cellRapid CommunicationRapid Communicationresearch-article20192019-01-01January 201910.1681/ASN.20180909121046-66731533-34502018-12-03T07:33:15-08:002019-01Journal of the American Society of NephrologyRapid Communication301233210.1681/ASN.2018060626Thu, 12 Jul 2018 05:24:21 GMT-07:00Single-Cell Sequencing the Glomerulus, Unraveling the Molecular Programs of Glomerular Filtration, One Cell at a TimeKretzler, MatthiasMenon, Rajasree2018-07-12T05:24:21-07:00doi:10.1681/ASN.2018060626hwp:resource-id:jnephrol;29/8/2036American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologySingle cell transcriptomics, glomerular disease, kidney diseaseUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20182018-08-01August 201810.1681/ASN.20180606261046-66731533-34502018-07-12T05:24:21-07:002018-08Journal of the American Society of NephrologyUp Front Matters29888203620602069203820682080Background Single-cell genomics techniques are revolutionizing our ability to characterize complex tissues. By contrast, the techniques used to analyze renal biopsy specimens have changed little over several decades. We tested the hypothesis that single-cell RNA-sequencing can comprehensively describe cell types and states in a human kidney biopsy specimen. Methods We generated 8746 single-cell transcriptomes from a healthy adult kidney and a single kidney transplant biopsy core by single-cell RNA-sequencing. Unsupervised clustering analysis of the biopsy specimen was performed to identify 16 distinct cell types, including all of the major immune cell types and most native kidney cell types, in this biopsy specimen, for which the histologic read was mixed rejection. Results Monocytes formed two subclusters representing a nonclassical CD16+ group and a classic CD16− group expressing dendritic cell maturation markers. The presence of both monocyte cell subtypes was validated by staining of independent transplant biopsy specimens. Comparison of healthy kidney epithelial transcriptomes with biopsy specimen counterparts identified novel segment-specific proinflammatory responses in rejection. Endothelial cells formed three distinct subclusters: resting cells and two activated endothelial cell groups. One activated endothelial cell group expressed Fc receptor pathway activation and Ig internalization genes, consistent with the pathologic diagnosis of antibody-mediated rejection. We mapped previously defined genes that associate with rejection outcomes to single cell types and generated a searchable online gene expression database. Conclusions We present the first step toward incorporation of single-cell transcriptomics into kidney biopsy specimen interpretation, describe a heterogeneous immune response in mixed rejection, and provide a searchable resource for the scientific community.10.1681/ASN.2018020125Fri, 06 Jul 2018 07:36:45 GMT-07:00Single-Cell Transcriptomics of a Human Kidney Allograft Biopsy Specimen Defines a Diverse Inflammatory ResponseBackground Single-cell genomics techniques are revolutionizing our ability to characterize complex tissues. By contrast, the techniques used to analyze renal biopsy specimens have changed little over several decades. We tested the hypothesis that single-cell RNA-sequencing can comprehensively describe cell types and states in a human kidney biopsy specimen. Methods We generated 8746 single-cell transcriptomes from a healthy adult kidney and a single kidney transplant biopsy core by single-cell RNA-sequencing. Unsupervised clustering analysis of the biopsy specimen was performed to identify 16 distinct cell types, including all of the major immune cell types and most native kidney cell types, in this biopsy specimen, for which the histologic read was mixed rejection. Results Monocytes formed two subclusters representing a nonclassical CD16+ group and a classic CD16− group expressing dendritic cell maturation markers. The presence of both monocyte cell subtypes was validated by staining of independent transplant biopsy specimens. Comparison of healthy kidney epithelial transcriptomes with biopsy specimen counterparts identified novel segment-specific proinflammatory responses in rejection. Endothelial cells formed three distinct subclusters: resting cells and two activated endothelial cell groups. One activated endothelial cell group expressed Fc receptor pathway activation and Ig internalization genes, consistent with the pathologic diagnosis of antibody-mediated rejection. We mapped previously defined genes that associate with rejection outcomes to single cell types and generated a searchable online gene expression database. Conclusions We present the first step toward incorporation of single-cell transcriptomics into kidney biopsy specimen interpretation, describe a heterogeneous immune response in mixed rejection, and provide a searchable resource for the scientific community.Wu, HaojiaMalone, Andrew F.Donnelly, Erinn L.Kirita, YuheiUchimura, KoheiRamakrishnan, Sai M.Gaut, Joseph P.Humphreys, Benjamin D.2018-07-06T07:36:45-07:00doi:10.1681/ASN.2018020125hwp:resource-id:jnephrol;29/8/2069American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, rejection, transcriptional profilingBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20180201251046-66731533-34502018-07-06T07:36:45-07:002018-08Journal of the American Society of NephrologyBasic Research29882069203620802038