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Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression.
Abedini, Amin; Levinsohn, Jonathan; Klötzer, Konstantin A; Dumoulin, Bernhard; Ma, Ziyuan; Frederick, Julia; Dhillon, Poonam; Balzer, Michael S; Shrestha, Rojesh; Liu, Hongbo; Vitale, Steven; Bergeson, Andi M; Devalaraja-Narashimha, Kishor; Grandi, Paola; Bhattacharyya, Tanmoy; Hu, Erding; Pullen, Steven S; Boustany-Kari, Carine M; Guarnieri, Paolo; Karihaloo, Anil; Traum, Daniel; Yan, Hanying; Coleman, Kyle; Palmer, Matthew; Sarov-Blat, Lea; Morton, Lori; Hunter, Christopher A; Kaestner, Klaus H; Li, Mingyao; Susztak, Katalin.
Afiliação
  • Abedini A; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Levinsohn J; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Klötzer KA; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Dumoulin B; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Ma Z; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Frederick J; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Dhillon P; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Balzer MS; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Shrestha R; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Liu H; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Vitale S; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Bergeson AM; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Devalaraja-Narashimha K; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Grandi P; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Bhattacharyya T; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Hu E; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Pullen SS; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Boustany-Kari CM; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Guarnieri P; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Karihaloo A; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Traum D; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Yan H; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Coleman K; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Palmer M; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Sarov-Blat L; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Morton L; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Hunter CA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Kaestner KH; Penn/CHOP Kidney Innovation Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
  • Li M; Nephrology, Charité - Universitätsmedizin, Berlin, Germany.
  • Susztak K; Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Nat Genet ; 56(8): 1712-1724, 2024 Aug.
Article em En | MEDLINE | ID: mdl-39048792
ABSTRACT
Kidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue. Unbiased deconvolution of the spatial data identifies the following four distinct microenvironments glomerular, immune, tubule and fibrotic. We describe the complex organization of microenvironments in health and disease and find that the fibrotic microenvironment is able to molecularly classify human kidneys and offers an improved prognosis compared to traditional histopathology. We provide a comprehensive spatially resolved molecular roadmap of the human kidney and the fibrotic process, demonstrating the clinical utility of spatial transcriptomics.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose / Progressão da Doença / Análise de Célula Única / Microambiente Celular / Rim / Nefropatias Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose / Progressão da Doença / Análise de Célula Única / Microambiente Celular / Rim / Nefropatias Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos