High-resolution Slide-seqV2 spatial transcriptomics enables discovery of disease-specific cell neighborhoods and pathways

iScience

Ayshwarya Subramanian¹  Katie Liguori²  Teia Noel³  Anna Greka⁴  Evan Z. Macosko⁴  Keith Keller⁵  Katherine A. Vernon⁶  Rowan M. Heneghan⁷  Evan Murray⁸  Qingbo S. Wang⁹  Jamie L. Marshall⁹  Fei Chen⁹  Breanna McBean⁹  Astrid Weins⁹  Silvana Bazua-Valenti^1,10  Haiqi Chen^1,11  Robert R. Stickels^1,12 

[1] Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA;Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;Corresponding author;Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA;Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan;Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;Program in Bioinformatics and Integrative Genomics, Harvard Medical School, Boston, MA 02115, USA;Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;Program in Cell Circuits and Epigenetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;

关键词: Pathophysiology;    Cell biology;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: High-resolution spatial transcriptomics enables mapping of RNA expression directly from intact tissue sections; however, its utility for the elucidation of disease processes and therapeutically actionable pathways remains unexplored. We applied Slide-seqV2 to mouse and human kidneys, in healthy and distinct disease paradigms. First, we established the feasibility of Slide-seqV2 in tissue from nine distinct human kidneys, which revealed a cell neighborhood centered around a population of LYVE1+ macrophages. Second, in a mouse model of diabetic kidney disease, we detected changes in the cellular organization of the spatially restricted kidney filter and blood-flow-regulating apparatus. Third, in a mouse model of a toxic proteinopathy, we identified previously unknown, disease-specific cell neighborhoods centered around macrophages. In a spatially restricted subpopulation of epithelial cells, we discovered perturbations in 77 genes associated with the unfolded protein response. Our studies illustrate and experimentally validate the utility of Slide-seqV2 for the discovery of disease-specific cell neighborhoods.

【 授权许可】

Unknown