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Transcriptional space-time mapping identifies concerted immune and stromal cell patterns and gene programs in wound healing and cancer
Cell Stem Cell ( IF 23.9 ) Pub Date : 2023-06-01 , DOI: 10.1016/j.stem.2023.05.001
Kenneth H Hu 1 , Nicholas F Kuhn 1 , Tristan Courau 2 , Jessica Tsui 3 , Bushra Samad 2 , Patrick Ha 4 , Johannes R Kratz 5 , Alexis J Combes 2 , Matthew F Krummel 1
Affiliation  

Tissue repair responses in metazoans are highly coordinated by different cell types over space and time. However, comprehensive single-cell-based characterization covering this coordination is lacking. Here, we captured transcriptional states of single cells over space and time during skin wound closure, revealing choreographed gene-expression profiles. We identified shared space-time patterns of cellular and gene program enrichment, which we call multicellular “movements” spanning multiple cell types. We validated some of the discovered space-time movements using large-volume imaging of cleared wounds and demonstrated the value of this analysis to predict “sender” and “receiver” gene programs in macrophages and fibroblasts. Finally, we tested the hypothesis that tumors are like “wounds that never heal” and found conserved wound healing movements in mouse melanoma and colorectal tumor models, as well as human tumor samples, revealing fundamental multicellular units of tissue biology for integrative studies.



中文翻译:

转录时空图谱识别伤口愈合和癌症中协调一致的免疫和基质细胞模式以及基因程序

后生动物的组织修复反应在空间和时间上由不同细胞类型高度协调。然而,缺乏涵盖这种协调的基于单细胞的全面表征。在这里,我们捕获了皮肤伤口闭合过程中单细胞随空间和时间的转录状态,揭示了精心设计的基因表达谱。我们确定了细胞和基因程序富集的共享时空模式,我们将其称为跨越多种细胞类型的多细胞“运动”。我们使用清理伤口的大体积成像验证了一些发现的时空运动,并证明了该分析在预测巨噬细胞和成纤维细胞中“发送者”和“接收者”基因程序的价值。最后,

更新日期:2023-06-01
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