美国哥伦比亚大学Azizi, Elham小组取得一项新突破。他们报道利用Starfysh整合空间转录组学和组织学数据，来揭示异质肿瘤免疫中心。相关论文于2024年3月21日发表在《自然—生物技术》杂志上。

空间分辨基因表达谱提供观察组织配置和细胞间交流的见解。然而，基于测序的空间转录组学(ST)缺乏单细胞分辨率。目前的空间转录组学分析方法需要单细胞RNA测序数据作为严格解释细胞状态的参考，大多数不涉及相关的组织学图像，也无法推断多个组织的共同邻近区域。

研究小组展示了Starfysh，一个以深度生成模型为主题的计算工具，该模型结合了原型分析和任何已知的细胞类型标记，以表征已知或新的组织特异性细胞状态，而无需单细胞参考。Starfysh用组织学图像改进了复杂组织的空间动力学特征，并使作为跨组织空间枢纽的生态位进行比较。对原发性雌激素受体(ER)阳性乳腺癌、三阴性乳腺癌(TNBC)和转移性乳腺癌(MBC)组织的综合分析，确定了具有患者和疾病特异性细胞类型组成的空间枢纽，并揭示了在侵润性MBC中形成免疫抑制中心的代谢重编程。

附：英文原文

Title: Starfysh integrates spatial transcriptomic and histologic data to reveal heterogeneous tumor–immune hubs

Author: He, Siyu, Jin, Yinuo, Nazaret, Achille, Shi, Lingting, Chen, Xueer, Rampersaud, Sham, Dhillon, Bahawar S., Valdez, Izabella, Friend, Lauren E., Fan, Joy Linyue, Park, Cameron Y., Mintz, Rachel L., Lao, Yeh-Hsing, Carrera, David, Fang, Kaylee W., Mehdi, Kaleem, Rohde, Madeline, McFaline-Figueroa, Jos L., Blei, David, Leong, Kam W., Rudensky, Alexander Y., Plitas, George, Azizi, Elham

Issue&Volume: 2024-03-21

Abstract: Spatially resolved gene expression profiling provides insight into tissue organization and cell–cell crosstalk; however, sequencing-based spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for rigorous interpretation of cell states, mostly do not use associated histology images and are not capable of inferring shared neighborhoods across multiple tissues. Here we present Starfysh, a computational toolbox using a deep generative model that incorporates archetypal analysis and any known cell type markers to characterize known or new tissue-specific cell states without a single-cell reference. Starfysh improves the characterization of spatial dynamics in complex tissues using histology images and enables the comparison of niches as spatial hubs across tissues. Integrative analysis of primary estrogen receptor (ER)-positive breast cancer, triple-negative breast cancer (TNBC) and metaplastic breast cancer (MBC) tissues led to the identification of spatial hubs with patient- and disease-specific cell type compositions and revealed metabolic reprogramming shaping immunosuppressive hubs in aggressive MBC.

DOI: 10.1038/s41587-024-02173-8

Source: https://www.nature.com/articles/s41587-024-02173-8