Departments of Medicine and Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
FASEB J. 2020 Mar;34(3):3519-3536. doi: 10.1096/fj.201903188R. Epub 2020 Feb 10.
The inherent plasticity and resiliency of fibroblasts make this cell type a conventional tool for basic research. But where do they come from, are all fibroblasts the same, and how do they function in disease? The first fibroblast lineages in mammalian development emerge from the ooze of primary mesenchyme during gastrulation. They are cells that efficiently create and negotiate the extracellular matrix of the mesoderm in order to migrate and meet their developmental fate. Mature fibroblasts in epithelial tissues live in the interstitial spaces between basement membranes that spatially delimit complex organ structures. While the function of resident fibroblasts in healthy tissues is largely conjecture, the accumulation of fibroblasts in pathologic lesions offers insight into biologic mechanisms that control their function; fibroblasts are poised to coordinate fibrogenesis in tissue injury, neoplasia, and aging. Here, we examine the developmental origin and plasticity of fibroblasts, their molecular and functional definitions, the epigenetic control underlying their identity and activation, and the evolution of their immune regulatory functions. These topics are reviewed through the lens of fate mapping using genetically engineered mouse models and from the perspective of single-cell RNA sequencing. Recent observations suggest dynamic and heterogeneous functions for fibroblasts that underscore their complex molecular signatures and utility in injured tissues.
成纤维细胞具有内在的可塑性和弹性，这使其成为基础研究的常规工具。但是，它们来自哪里，是否所有成纤维细胞都相同，以及它们在疾病中如何发挥作用？哺乳动物发育过程中的第一批成纤维细胞谱系源自原肠胚形成过程中初级间质的糊状物。它们是能够有效地创建和协商中胚层细胞外基质的细胞，以便迁移并满足其发育命运。上皮组织中的成熟成纤维细胞生活在空间上分隔复杂器官结构的基底膜之间的间质空间中。虽然健康组织中驻留成纤维细胞的功能在很大程度上是推测性的，但病理损伤中成纤维细胞的积累为控制其功能的生物学机制提供了深入了解；成纤维细胞有望协调组织损伤、肿瘤发生和衰老中的纤维生成。在这里，我们研究了成纤维细胞的发育起源和可塑性、它们的分子和功能定义、控制其身份和激活的表观遗传控制，以及它们免疫调节功能的进化。这些主题是通过使用基因工程小鼠模型进行的命运图谱研究以及单细胞 RNA 测序的角度进行审查的。最近的观察结果表明，成纤维细胞具有动态和异质的功能，这突出了它们复杂的分子特征及其在受损组织中的应用。
