Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell Stem Cell. 2023 Jun 1;30(6):885-903.e10. doi: 10.1016/j.stem.2023.05.001.
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.
多细胞生物的组织修复反应在空间和时间上受到不同细胞类型的高度协调。然而,全面的单细胞基础特征涵盖这种协调还很缺乏。在这里,我们在皮肤伤口闭合过程中捕获了单细胞的转录状态,揭示了精心编排的基因表达谱。我们确定了细胞和基因程序富集的共享时空模式,我们称之为跨越多个细胞类型的多细胞“运动”。我们使用清除伤口的大容量成像验证了一些发现的时空运动,并证明了这种分析对于预测巨噬细胞和成纤维细胞中“发送器”和“接收器”基因程序的价值。最后,我们检验了肿瘤就像“永不愈合的伤口”这一假说,并在小鼠黑色素瘤和结直肠癌肿瘤模型以及人类肿瘤样本中发现了保守的伤口愈合运动,揭示了组织生物学的基本多细胞单元,用于综合研究。