TY - JOUR
T1 - Resident macrophage subpopulations occupy distinct microenvironments in the kidney
AU - Cheung, Matthew D.
AU - Erman, Elise N.
AU - Moore, Kyle H.
AU - Lever, Jeremie M.P.
AU - Li, Zhang
AU - LaFontaine, Jennifer R.
AU - Ghajar-Rahimi, Gelare
AU - Liu, Shanrun
AU - Yang, Zhengqin
AU - Karim, Rafay
AU - Yoder, Bradley K.
AU - Agarwal, Anupam
AU - George, James F.
N1 - Publisher Copyright:
© 2022, Cheung et al.
PY - 2022/10/24
Y1 - 2022/10/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85140417817&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.161078
DO - 10.1172/jci.insight.161078
M3 - Article
C2 - 36066976
AN - SCOPUS:85140417817
SN - 2379-3708
VL - 7
JO - JCI insight
JF - JCI insight
IS - 20
M1 - e161078
ER -