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Melo Ferreira R, Sabo AR, Winfree S, et al. Integration of spatial and single-cell transcriptomics localizes epithelial cell-immune cross-talk in kidney injury. JCI Insight. 2021;6(12)doi: 10.1172/jci.insight.147703.
Melo Ferreira, R., Sabo, A. R., Winfree, S., Collins, K. S., Janosevic, D., Gulbronson, C. J., Cheng, Y. H., Casbon, L., Barwinska, D., Ferkowicz, M. J., Xuei, X., Zhang, C., Dunn, K. W., Kelly, K. J., Sutton, T. A., Hato, T., Dagher, P. C., El-Achkar, T. M., & Eadon, M. T. (2021). Integration of spatial and single-cell transcriptomics localizes epithelial cell-immune cross-talk in kidney injury. JCI insight, 6(12), . https://doi.org/10.1172/jci.insight.147703
Melo Ferreira, Ricardo, et al. "Integration of spatial and single-cell transcriptomics localizes epithelial cell-immune cross-talk in kidney injury." JCI insight vol. 6,12 (2021). doi: https://doi.org/10.1172/jci.insight.147703
Melo Ferreira R, Sabo AR, Winfree S, Collins KS, Janosevic D, Gulbronson CJ, Cheng YH, Casbon L, Barwinska D, Ferkowicz MJ, Xuei X, Zhang C, Dunn KW, Kelly KJ, Sutton TA, Hato T, Dagher PC, El-Achkar TM, Eadon MT. Integration of spatial and single-cell transcriptomics localizes epithelial cell-immune cross-talk in kidney injury. JCI Insight. 2021 Jun 22;6(12). doi: 10.1172/jci.insight.147703. PMID: 34003797; PMCID: PMC8262485.
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JCI Insight. 2021 Jun 22;6(12). doi: 10.1172/jci.insight.147703.

Integration of spatial and single-cell transcriptomics localizes epithelial cell-immune cross-talk in kidney injury.

JCI insight

Ricardo Melo Ferreira, Angela R Sabo, Seth Winfree, Kimberly S Collins, Danielle Janosevic, Connor J Gulbronson, Ying-Hua Cheng, Lauren Casbon, Daria Barwinska, Michael J Ferkowicz, Xiaoling Xuei, Chi Zhang, Kenneth W Dunn, Katherine J Kelly, Timothy A Sutton, Takashi Hato, Pierre C Dagher, Tarek M El-Achkar, Michael T Eadon

Affiliations

  1. Department of Medicine and.
  2. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.

PMID: 34003797 PMCID: PMC8262485 DOI: 10.1172/jci.insight.147703

Abstract

Single-cell sequencing studies have characterized the transcriptomic signature of cell types within the kidney. However, the spatial distribution of acute kidney injury (AKI) is regional and affects cells heterogeneously. We first optimized coordination of spatial transcriptomics and single-nuclear sequencing data sets, mapping 30 dominant cell types to a human nephrectomy. The predicted cell-type spots corresponded with the underlying histopathology. To study the implications of AKI on transcript expression, we then characterized the spatial transcriptomic signature of 2 murine AKI models: ischemia/reperfusion injury (IRI) and cecal ligation puncture (CLP). Localized regions of reduced overall expression were associated with injury pathways. Using single-cell sequencing, we deconvoluted the signature of each spatial transcriptomic spot, identifying patterns of colocalization between immune and epithelial cells. Neutrophils infiltrated the renal medulla in the ischemia model. Atf3 was identified as a chemotactic factor in S3 proximal tubules. In the CLP model, infiltrating macrophages dominated the outer cortical signature, and Mdk was identified as a corresponding chemotactic factor. The regional distribution of these immune cells was validated with multiplexed CO-Detection by indEXing (CODEX) immunofluorescence. Spatial transcriptomic sequencing complemented single-cell sequencing by uncovering mechanisms driving immune cell infiltration and detection of relevant cell subpopulations.

Keywords: Expression profiling; Mouse models; Nephrology

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