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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2022
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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. |
format | Online Article Text |
id | pubmed-9714795 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
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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