| Autor: |
Melo Ferreira R; Department of Medicine and., Sabo AR; Department of Medicine and., Winfree S; Department of Medicine and., Collins KS; Department of Medicine and., Janosevic D; Department of Medicine and., Gulbronson CJ; Department of Medicine and., Cheng YH; Department of Medicine and., Casbon L; Department of Medicine and., Barwinska D; Department of Medicine and., Ferkowicz MJ; Department of Medicine and., Xuei X; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Zhang C; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Dunn KW; Department of Medicine and., Kelly KJ; Department of Medicine and., Sutton TA; Department of Medicine and., Hato T; Department of Medicine and., Dagher PC; Department of Medicine and., El-Achkar TM; Department of Medicine and., Eadon MT; Department of Medicine and.; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA. |
| Abstrakt: |
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. |
