Transcriptomic characterisation of transitioning cell types in the skin of Atlantic salmon

Background The skin maintains the body's integrity and serves as the first line of defence against pathogens, stressors and mechanical injuries. Despite the global significance of salmon in aquaculture, how cells transcriptomic profile varies during wound healing, remains unexplored. Teleost contain adult pluripotent cells that differentiate into various tissues, including bone, cartilage, tendon, ligament, adipose, dermis, muscle and connective tissue within the skin. These cells are pivotal for preserving the integrity of skin tissue throughout an organism´s lifespan and actively participate in the wound healing processes. In this study, we characterise the transcriptomic profiles of putative mesenchymal stromal cells (fibroblast-like adult stem cells) in healthy Atlantic salmon tissue and during the wound healing process. Results Single-nucleus sequencing and spatial transcriptomics were used to detect transcriptomic changes occurring during wound healing that are commonly associated with mesenchymal stromal cells. We followed the transcriptomic activity of these cells during an in vivo wound healing time course study showing that these cells become more transcriptionally active during the remodelling stage of wound healing. The changes detected give insights into the potential differentiation pathways leading to osteogenic and fibroblast lineages in the skin of Atlantic salmon. Conclusions We chart the transcriptomic activity of sub-clusters of putative differentiating stromal cells during the process of wound healing for the first time, revealing different spatial niches of the various putative MSC subclusters, and setting the stage for further investigation of the manipulation of transitioning cell types to improve fish health. KEYWORDS: Salmo salar, skin, mesenchymal stromal cells, single-cell sequencing, spatial transcriptomics, wound healing, spatial niche. Overall design: Skin from both the body and fins of Atlantic salmon (Salmo salar) was analyzed using snRNA-seq.

研究背景：皮肤是维持机体完整性的核心屏障，亦是抵御病原体、应激源与机械损伤的第一道防线。尽管鲑鱼在水产养殖领域具有全球战略重要性，但目前学界尚未阐明伤口愈合过程中细胞转录组谱的动态变化规律。硬骨鱼类（Teleost）体内存在成体多能细胞，可分化为皮肤内的多种组织类型，包括骨、软骨、肌腱、韧带、脂肪、真皮、肌肉与结缔组织。这类细胞对于维持机体终生皮肤组织的完整性至关重要，且积极参与伤口愈合的各个环节。本研究对健康大西洋鲑组织及伤口愈合过程中推定的间充质基质细胞（mesenchymal stromal cells，成纤维细胞样成体干细胞）的转录组谱进行了系统表征。
研究结果：本研究采用单细胞核测序与空间转录组学技术，检测了伤口愈合过程中与间充质基质细胞相关的典型转录组变化。通过体内伤口愈合时间序列实验，我们追踪了这类细胞的转录组活性动态，发现其在伤口愈合的重塑阶段转录活性显著上调。本研究揭示的转录组变化为大西洋鲑皮肤内成骨细胞系与成纤维细胞系的潜在分化通路提供了全新的研究视角。
研究结论：本研究首次系统描绘了伤口愈合过程中推定的分化性基质细胞亚群的转录组活性谱，揭示了不同推定间充质基质细胞（mesenchymal stromal cells，以下简称MSCs）亚群的独特空间龛位，并为后续通过调控细胞类型转化以提升鱼类健康的研究奠定了坚实基础。
关键词：大西洋鲑（Salmo salar）、皮肤、间充质基质细胞、单细胞核测序、空间转录组学、伤口愈合、空间龛位。
实验设计：本研究采用单细胞核RNA测序（snRNA-seq）技术，对大西洋鲑（Salmo salar）体部与鳍部的皮肤组织进行了转录组分析。