Spatially resolved transcriptome profiles of mammalian kidneys illustrate the molecular complexity of functional nephron segments, cell-to-cell interactions and genetic variants

Author:

Raghubar Arti M.,Pham Duy T.,Tan Xiao,Grice Laura F.,Crawford Joanna,Lam Pui Yeng,Andersen Stacey B.,Yoon Sohye,Ng Monica S.Y.,Teoh Siok Min,Holland Samuel E.,Stewart Anne,Francis Leo,Combes Alexander N.,Kassianos Andrew J.,Healy Helen,Nguyen Quan,Mallett Andrew J.

Abstract

AbstractUnderstanding the molecular mechanisms underlying mammalian kidney function requires transcriptome profiling of the interplay between cells comprising nephron segments. Traditional transcriptomics requires cell dissociation, resulting in loss of the spatial context of gene expression within native tissue. To address this problem, we performed spatial transcriptomics (ST) to retain the spatial context of the transcriptome in human and mouse kidneys. The generated ST data allowed spatially resolved differential gene expression analysis, spatial identification of functional nephron segments, cell-to-cell interaction analysis, and chronic kidney disease-associated genetic variant calling. Novel ST thus provides an opportunity to enhance kidney diagnostics and knowledge, by retaining the spatial context of gene expression within intact tissue.

Publisher

Cold Spring Harbor Laboratory

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