Spotiphy enables single-cell spatial whole transcriptomics across an entire section

被引：1

作者：

Yang, Jiyuan ^{[1
]}

Zheng, Ziqian ^{[2
]}

Jiao, Yun ^{[3
]}

Yu, Kaiwen ^{[4
]}

Bhatara, Sheetal ^{[1
]}

Yang, Xu ^{[1
]}

Natarajan, Sivaraman ^{[1
]}

Zhang, Jiahui ^{[2
]}

Pan, Qingfei ^{[1
]}

Easton, John ^{[1
]}

Yan, Koon-Kiu ^{[1
]}

Peng, Junmin ^{[3
]}

Liu, Kaibo ^{[2
]}

Yu, Jiyang ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA

[2] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA

[3] St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA

[4] St Jude Childrens Res Hosp, Ctr Prote & Metabol, Memphis, TN USA

来源：

NATURE METHODS | 2025年 / 22卷 / 04期

基金：

美国国家卫生研究院;

关键词：

RNA-SEQ; MICROGLIA; EXPRESSION; ATLAS; HETEROGENEITY;

D O I：

10.1038/s41592-025-02622-5

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization of gene expression within whole-tissue sections, but current approaches remain plagued by the challenge of achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome images. Spotiphy delivers the most precise cellular proportions in extensive benchmarking evaluations. Spotiphy-derived inferred single-cell profiles reveal astrocyte and disease-associated microglia regional specifications in Alzheimer's disease and healthy mouse brains. Spotiphy identifies multiple spatial domains and alterations in tumor-tumor microenvironment interactions in human breast ST data. Spotiphy bridges the information gap and enables visualization of cell localization and transcriptomic profiles throughout entire sections, offering highly informative outputs and an innovative spatial analysis pipeline for exploring complex biological systems.

引用

页码：724 / 736

页数：32

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