美国加州大学Matthew F. Krummel、Kenneth H. Hu研究小组的最新研究揭示转录时空映射识别伤口愈合和癌症中的协同免疫、基质细胞模式和基因程序。2023年6月1日，国际学术期刊《细胞—干细胞》发表了这一成果。

研究人员获得了皮肤伤口闭合过程中单细胞在空间和时间上的转录状态，揭示了精密的基因表达谱。研究确定了细胞和基因程序富集的共享时空模式，称之为跨越多种细胞类型的多细胞“运动”。研究人员使用清除伤口的大体积成像验证了一些已经发现的时空运动，并证明了该分析在预测巨噬细胞和成纤维细胞“发送者”和“接收者”基因程序的价值。最后，研究人员测试了肿瘤像“永不愈合伤口”的假设，并在小鼠黑色素瘤和结直肠肿瘤模型以及人肿瘤样本中发现了这种保守的伤口愈合运动，揭示了组织生物学的多细胞单位可用于综合研究。

据介绍，后生动物的组织修复反应是由时间和空间上的不同细胞类型高度协调完成。然而，缺乏全面涵盖这种协调的基于单细胞的表征。

附：英文原文

Title: Transcriptional space-time mapping identifies concerted immune and stromal cell patterns and gene programs in wound healing and cancer

Author: Kenneth H. Hu, Nicholas F. Kuhn, Tristan Courau, Jessica Tsui, Bushra Samad, Patrick Ha, Johannes R. Kratz, Alexis J. Combes, Matthew F. Krummel

Issue&Volume: 2023/06/01

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

DOI: 10.1016/j.stem.2023.05.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00171-6