Mapping human tissues with highly multiplexed RNA in situ hybridization

Kian Kalhor, Chien Ju Chen, Ho Suk Lee, Matthew Cai, Mahsa Nafisi, Richard Que, Carter R. Palmer, Yixu Yuan, Yida Zhang, Xuwen Li, Jinghui Song, Amanda Knoten, Blue B. Lake, Joseph P. Gaut, C. Dirk Keene, Ed Lein, Peter V. Kharchenko, Jerold Chun, Sanjay Jain, Jian Bing FanKun Zhang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in <10 h. We successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.

Original languageEnglish
Article number2511
JournalNature communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

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