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Resident macrophage subpopulations occupy distinct microenvironments in the kidney

The kidney contains a population of resident macrophages from birth that expands as it grows and forms a contiguous network throughout the tissue. Kidney-resident macrophages (KRMs) are important in homeostasis and the response to acute kidney injury. While the kidney contains many microenvironments...

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Autores principales: Cheung, Matthew D., Erman, Elise N., Moore, Kyle H., Lever, Jeremie M.P., Li, Zhang, LaFontaine, Jennifer R., Ghajar-Rahimi, Gelare, Liu, Shanrun, Yang, Zhengqin, Karim, Rafay, Yoder, Bradley K., Agarwal, Anupam, George, James F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714795/
https://www.ncbi.nlm.nih.gov/pubmed/36066976
http://dx.doi.org/10.1172/jci.insight.161078
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author Cheung, Matthew D.
Erman, Elise N.
Moore, Kyle H.
Lever, Jeremie M.P.
Li, Zhang
LaFontaine, Jennifer R.
Ghajar-Rahimi, Gelare
Liu, Shanrun
Yang, Zhengqin
Karim, Rafay
Yoder, Bradley K.
Agarwal, Anupam
George, James F.
author_facet Cheung, Matthew D.
Erman, Elise N.
Moore, Kyle H.
Lever, Jeremie M.P.
Li, Zhang
LaFontaine, Jennifer R.
Ghajar-Rahimi, Gelare
Liu, Shanrun
Yang, Zhengqin
Karim, Rafay
Yoder, Bradley K.
Agarwal, Anupam
George, James F.
author_sort Cheung, Matthew D.
collection PubMed
description The kidney contains a population of resident macrophages from birth that expands as it grows and forms a contiguous network throughout the tissue. Kidney-resident macrophages (KRMs) are important in homeostasis and the response to acute kidney injury. While the kidney contains many microenvironments, it is unknown whether KRMs are a heterogeneous population differentiated by function and location. We combined single-cell RNA-Seq (scRNA-Seq), spatial transcriptomics, flow cytometry, and immunofluorescence imaging to localize, characterize, and validate KRM populations during quiescence and following 19 minutes of bilateral ischemic kidney injury. scRNA-Seq and spatial transcriptomics revealed 7 distinct KRM subpopulations, which are organized into zones corresponding to regions of the nephron. Each subpopulation was identifiable by a unique transcriptomic signature, suggesting distinct functions. Specific protein markers were identified for 2 clusters, allowing analysis by flow cytometry or immunofluorescence imaging. Following injury, the original localization of each subpopulation was lost, either from changing locations or transcriptomic signatures. The original spatial distribution of KRMs was not fully restored for at least 28 days after injury. The change in KRM localization confirmed a long-hypothesized dysregulation of the local immune system following acute injury and may explain the increased risk for chronic kidney disease.
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spelling pubmed-97147952022-12-04 Resident macrophage subpopulations occupy distinct microenvironments in the kidney Cheung, Matthew D. Erman, Elise N. Moore, Kyle H. Lever, Jeremie M.P. Li, Zhang LaFontaine, Jennifer R. Ghajar-Rahimi, Gelare Liu, Shanrun Yang, Zhengqin Karim, Rafay Yoder, Bradley K. Agarwal, Anupam George, James F. JCI Insight Technical Advance The kidney contains a population of resident macrophages from birth that expands as it grows and forms a contiguous network throughout the tissue. Kidney-resident macrophages (KRMs) are important in homeostasis and the response to acute kidney injury. While the kidney contains many microenvironments, it is unknown whether KRMs are a heterogeneous population differentiated by function and location. We combined single-cell RNA-Seq (scRNA-Seq), spatial transcriptomics, flow cytometry, and immunofluorescence imaging to localize, characterize, and validate KRM populations during quiescence and following 19 minutes of bilateral ischemic kidney injury. scRNA-Seq and spatial transcriptomics revealed 7 distinct KRM subpopulations, which are organized into zones corresponding to regions of the nephron. Each subpopulation was identifiable by a unique transcriptomic signature, suggesting distinct functions. Specific protein markers were identified for 2 clusters, allowing analysis by flow cytometry or immunofluorescence imaging. Following injury, the original localization of each subpopulation was lost, either from changing locations or transcriptomic signatures. The original spatial distribution of KRMs was not fully restored for at least 28 days after injury. The change in KRM localization confirmed a long-hypothesized dysregulation of the local immune system following acute injury and may explain the increased risk for chronic kidney disease. American Society for Clinical Investigation 2022-10-24 /pmc/articles/PMC9714795/ /pubmed/36066976 http://dx.doi.org/10.1172/jci.insight.161078 Text en © 2022 Cheung et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Technical Advance
Cheung, Matthew D.
Erman, Elise N.
Moore, Kyle H.
Lever, Jeremie M.P.
Li, Zhang
LaFontaine, Jennifer R.
Ghajar-Rahimi, Gelare
Liu, Shanrun
Yang, Zhengqin
Karim, Rafay
Yoder, Bradley K.
Agarwal, Anupam
George, James F.
Resident macrophage subpopulations occupy distinct microenvironments in the kidney
title Resident macrophage subpopulations occupy distinct microenvironments in the kidney
title_full Resident macrophage subpopulations occupy distinct microenvironments in the kidney
title_fullStr Resident macrophage subpopulations occupy distinct microenvironments in the kidney
title_full_unstemmed Resident macrophage subpopulations occupy distinct microenvironments in the kidney
title_short Resident macrophage subpopulations occupy distinct microenvironments in the kidney
title_sort resident macrophage subpopulations occupy distinct microenvironments in the kidney
topic Technical Advance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714795/
https://www.ncbi.nlm.nih.gov/pubmed/36066976
http://dx.doi.org/10.1172/jci.insight.161078
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