Abstract：
The molecular and cellular basis of health in human tendons remains poorly understood. Among human tendons, hamstring tendon has markedly low pathology and can provide a prototypic healthy tendon reference. The aim of this study was to determine the transcriptomes and location of all cell types in healthy hamstring tendon. Using single nucleus RNA sequencing, we profiled the transcriptomes of 10 533 nuclei from four healthy donors and identified 12 distinct cell types. We confirmed the presence of two fibroblast cell types, endothelial cells, mural cells, and immune cells, and identified cell types previously unreported in tendons, including different skeletal muscle cell types, satellite cells, adipocytes, and undefined nervous system cells. The location of these cell types within tendon was defined using spatial transcriptomics and imaging, and potential transcriptional networks and cell-cell interactions were analyzed. We demonstrate that fibroblasts have the highest number of potential cell-cell interactions in our dataset, are present throughout the tendon, and play an important role in the production and organization of extracellular matrix, thus confirming their role as key regulators of hamstring tendon homeostasis. Overall, our findings underscore the complexity of the cellular networks that underpin healthy human tendon function and the central role of fibroblasts as key regulators of hamstring tendon tissue homeostasis.
摘要：
人类肌腱健康的分子和细胞基础仍然知之甚少。在人类肌腱中，腿筋肌腱具有明显的低病理，可以提供原型健康的肌腱参考。这项研究的目的是确定健康绳肌腱中所有细胞类型的转录组和位置。使用单核RNA测序，我们对来自四个健康供体的10533个细胞核的转录组进行了分析，并鉴定了12种不同的细胞类型。我们证实了两种成纤维细胞类型的存在，内皮细胞，壁细胞,和免疫细胞，并确定了肌腱中以前未报告的细胞类型，包括不同的骨骼肌细胞类型，卫星细胞,脂肪细胞,和未定义的神经系统细胞。使用空间转录组学和成像来确定肌腱中这些细胞类型的位置，并分析了潜在的转录网络和细胞间的相互作用。我们证明，成纤维细胞在我们的数据集中具有最高数量的潜在细胞-细胞相互作用，存在于整个肌腱中，并在细胞外基质的产生和组织中起重要作用，从而证实了他们作为腿筋肌腱稳态的关键调节剂的作用。总的来说,我们的研究结果强调了支撑健康人肌腱功能的细胞网络的复杂性,以及成纤维细胞作为腿筋肌腱组织稳态的关键调节因子的中心作用.
