Spatiotemporal single-cell roadmap of human skin wound healing

IF 19.8 1区医学 Q1 CELL & TISSUE ENGINEERING

Cell stem cell Pub Date : 2024-12-26 DOI:10.1016/j.stem.2024.11.013

Zhuang Liu, Xiaowei Bian, Lihua Luo, Åsa K. Björklund, Li Li, Letian Zhang, Yongjian Chen, Lei Guo, Juan Gao, Chunyan Cao, Jiating Wang, Wenjun He, Yunting Xiao, Liping Zhu, Karl Annusver, Nusayhah Hudaa Gopee, Daniela Basurto-Lozada, David Horsfall, Clare L. Bennett, Maria Kasper, Ning Xu Landén

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引用次数: 0

Abstract

Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell multi-omics analyses on human skin wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations.

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人体皮肤伤口愈合的时空单细胞路线图

伤口愈合对人类健康至关重要，但细胞动力学和人体伤口修复协调的细节仍未得到充分研究。为了解决这个问题，我们对来自同一个体的人类皮肤伤口组织进行了单细胞多组学分析，包括伤口修复的炎症、增殖和重塑阶段，以前所未有的时空分辨率监测人类皮肤伤口愈合的细胞和分子动力学。这一独特的路线图揭示了创面边缘的细胞结构，并确定了FOSL1是再上皮化的关键驱动因素。这表明促炎巨噬细胞和成纤维细胞在不同愈合阶段先后支持角质形成细胞的迁移，就像接力赛一样。与静脉和糖尿病足溃疡单细胞数据的比较揭示了慢性伤口中角化细胞迁移失败和炎症反应受损之间的联系。此外，比较人类和小鼠急性伤口转录组强调了该路线图在连接基础研究与临床创新方面不可或缺的价值。

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来源期刊

Cell stem cell 生物-细胞生物学

CiteScore

37.10

自引率

2.50%

发文量

151

审稿时长

42 days

期刊介绍： Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.