Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford, CA 94305, USA.
Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dis Model Mech. 2020 Jun 15;13(6):dmm044164. doi: 10.1242/dmm.044164.
Tissue fibrosis is the deposition of excessive extracellular matrix and can occur as part of the body's natural wound healing process upon injury, or as a consequence of diseases such as systemic sclerosis. Skin fibrosis contributes to significant morbidity due to the prevalence of injuries resulting from trauma and burn. Fibroblasts, the principal cells of the dermis, synthesize extracellular matrix to maintain the skin during homeostasis and also play a pivotal role in all stages of wound healing. Although it was previously believed that fibroblasts are homogeneous and mostly quiescent cells, it has become increasingly recognized that numerous fibroblast subtypes with unique functions and morphologies exist. This Review provides an overview of fibroblast heterogeneity in the mammalian dermis. We explain how fibroblast identity relates to their developmental origin, anatomical site and precise location within the skin tissue architecture in both human and mouse dermis. We discuss current evidence for the varied functionality of fibroblasts within the dermis and the relationships between fibroblast subtypes, and explain the current understanding of how fibroblast subpopulations may be controlled through transcriptional regulatory networks and paracrine communications. We consider how fibroblast heterogeneity can influence wound healing and fibrosis, and how insight into fibroblast heterogeneity could lead to novel therapeutic developments and targets for skin fibrosis. Finally, we contemplate how future studies should be shaped to implement knowledge of fibroblast heterogeneity into clinical practice in order to lessen the burden of skin fibrosis.
组织纤维化是细胞外基质的过度沉积，可作为机体受伤后天然愈合过程的一部分发生，也可作为系统性硬皮病等疾病的后果发生。皮肤纤维化会导致严重的发病率，因为创伤和烧伤导致的损伤很常见。成纤维细胞是真皮的主要细胞，它在维持皮肤内环境稳定时合成细胞外基质，并在伤口愈合的所有阶段发挥关键作用。尽管以前认为成纤维细胞是同质的、大多处于静止状态的细胞，但越来越多的证据表明，存在许多具有独特功能和形态的成纤维细胞亚型。这篇综述概述了哺乳动物真皮中成纤维细胞的异质性。我们解释了成纤维细胞的身份与其发育起源、解剖部位以及在人和小鼠真皮组织架构中的精确位置之间的关系。我们讨论了目前关于真皮内成纤维细胞功能多样性的证据，以及成纤维细胞亚型之间的关系，并解释了目前对成纤维细胞亚群如何通过转录调控网络和旁分泌通讯进行控制的理解。我们考虑了成纤维细胞异质性如何影响伤口愈合和纤维化，以及深入了解成纤维细胞异质性如何为皮肤纤维化的治疗提供新的发展和靶点。最后，我们思考未来的研究应该如何进行，以便将成纤维细胞异质性的知识应用于临床实践，从而减轻皮肤纤维化的负担。
