The largest mammalian organ, skin, consisting of a dermal connective tissue layer that underlies and supports the epidermis, acts as a protective barrier that excludes external pathogens and disseminates sensory signals emanating from the local microenvironment. Dermal connective tissue is comprised of a collagen-rich extracellular matrix (ECM) that is produced by connective tissue fibroblasts resident within the dermis. When wounded, a tissue repair program is induced whereby fibroblasts, in response to alterations in the microenvironment, produce new ECM components, resulting in the formation of a scar. Failure to terminate the normal tissue repair program causes fibrotic conditions including: hypertrophic scars, keloids, and the systemic autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc). Histological and single-cell RNA sequencing (scRNAseq) studies have revealed that fibroblasts are heterogeneous and highly plastic. Understanding how this diversity contributes to dermal homeostasis, wounding, fibrosis, and cancer may ultimately result in novel anti-fibrotic therapies and personalized medicine. This review summarizes studies supporting this concept.

中文翻译：

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位置信息在确定真皮成纤维细胞多样性中的作用


皮肤是哺乳动物最大的器官，由位于表皮下方并支撑表皮的真皮结缔组织层组成，充当保护屏障，排除外部病原体并传播来自局部微环境的感觉信号。真皮结缔组织由富含胶原蛋白的细胞外基质 (ECM) 组成，该基质是由真皮内的结缔组织成纤维细胞产生的。受伤时，会诱导组织修复程序，成纤维细胞响应微环境的变化，产生新的 ECM 成分，从而形成疤痕。未能终止正常组织修复程序会导致纤维化病症，包括：肥厚性疤痕、疤痕疙瘩和系统性自身免疫性结缔组织病硬皮病（系统性硬化症，SSc）。组织学和单细胞 RNA 测序 (scRNAseq) 研究表明，成纤维细胞具有异质性和高度可塑性。了解这种多样性如何影响真皮稳态、伤口、纤维化和癌症可能最终会产生新的抗纤维化疗法和个性化医疗。这篇综述总结了支持这一概念的研究。