Tendon is a dense connective tissue that stores and transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, yet little is known about the diversity of cell types that populate tendon. To address this, we determined the heterogeneity of cell populations within mouse Achilles tendons using single-cell RNA sequencing. In assembling a transcriptomic atlas of Achilles tendons, we identified 11 distinct types of cells, including 3 previously undescribed populations of tendon fibroblasts. Prior studies have indicated that pericytes, which are found in the vasculature of tendons, could serve as a potential source of progenitor cells for adult tendon fibroblasts. Using trajectory inference analysis, we provide additional support for the notion that pericytes are likely to be at least one of the progenitor cell populations for the fibroblasts that compose adult tendons. We also modeled cell-cell interactions and identified previously undescribed ligand-receptor signaling interactions involved in tendon homeostasis. Our novel and interactive tendon atlas highlights previously underappreciated heterogeneity between and within tendon cell populations. The atlas also serves as a resource to further the understanding of tendon extracellular matrix assembly, maintenance, and in the design of therapies for tendinopathies.

中文翻译：

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单细胞转录组学分析确定了小鼠跟腱细胞组成中的广泛异质性。

肌腱是一种致密的结缔组织，可在肌肉和骨骼之间储存和传递力。细胞异质性越来越被认为是组织稳态和疾病生物学基础的重要因素，但对肌腱细胞类型的多样性知之甚少。为了解决这个问题，我们使用单细胞 RNA 测序确定了小鼠跟腱内细胞群的异质性。在组装跟腱转录组图谱时，我们确定了 11 种不同类型的细胞，包括 3 种以前未描述的肌腱成纤维细胞群。先前的研究表明，在肌腱的脉管系统中发现的周细胞可以作为成人肌腱成纤维细胞的祖细胞的潜在来源。使用轨迹推断分析，我们对周细胞可能是构成成人肌腱的成纤维细胞的至少一种祖细胞群的观点提供了额外的支持。我们还模拟了细胞 - 细胞相互作用，并确定了以前未描述的参与肌腱稳态的配体 - 受体信号相互作用。我们新颖的交互式肌腱图谱突出了以前被低估的肌腱细胞群之间和内部的异质性。该图谱还可以作为进一步了解肌腱细胞外基质组装、维护和肌腱病疗法设计的资源。我们还模拟了细胞 - 细胞相互作用，并确定了以前未描述的参与肌腱稳态的配体 - 受体信号相互作用。我们新颖的交互式肌腱图谱突出了以前被低估的肌腱细胞群之间和内部的异质性。该图谱还可以作为进一步了解肌腱细胞外基质组装、维护和肌腱病疗法设计的资源。我们还模拟了细胞 - 细胞相互作用，并确定了以前未描述的参与肌腱稳态的配体 - 受体信号相互作用。我们新颖的交互式肌腱图谱突出了以前被低估的肌腱细胞群之间和内部的异质性。该图谱还可以作为进一步了解肌腱细胞外基质组装、维护和肌腱病疗法设计的资源。