Distinct fibroblast lineages determine dermal architecture in skin development and repair.
Distinct fibroblast lineages determine dermal architecture in skin development and repair.
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作者：
成纤维细胞是结缔组织中主要的间充质细胞类型，能沉积细胞外基质（ECM）中的胶原蛋白和弹性纤维。即使在单一组织内，成纤维细胞也表现出显著的功能多样性，但尚不清楚这是反映了分化层级的存在，还是对不同环境因素的反应。在此，我们通过移植实验和谱系追踪表明，皮肤结缔组织的成纤维细胞来自两个不同的谱系。一个形成真皮上层，包括调节毛发生长的毛乳头和控制立毛的立毛肌（APM）。另一个形成真皮下层，包括合成大部分纤维状ECM的网状成纤维细胞，以及皮下组织的前脂肪细胞和脂肪细胞。真皮上层谱系是毛囊形成所必需的。在受伤的成年皮肤中，真皮修复的初始波由真皮下层谱系介导，真皮上层成纤维细胞仅在再上皮化过程中被募集。表皮β -连环蛋白的激活刺激真皮上层谱系的扩增，使伤口有利于毛囊形成。我们的研究结果解释了为什么创伤与缺乏毛囊且富含ECM的瘢痕组织的形成有关。它们也为发现其他组织中的成纤维细胞谱系以及研究衰老和疾病过程中成纤维细胞的变化提供了一个平台。
Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibers of the extracellular matrix (ECM). Even within a single tissue fibroblasts exhibit remarkable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle (APM), which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesise the bulk of the fibrillar ECM, and the pre-adipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialisation. Epidermal beta-catenin activation stimulates expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles. They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.
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影响因子：
7.8
作者：
Giangreco A;Qin M;Pintar JE;Watt FM
通讯作者：
Watt FM
表皮包括由不同的干细胞种群维持的自主室。
影响因子：
23.9
作者：
Page, Mahalia E.;Lombard, Patrick;Ng, Felicia;Goettgens, Berthold;Jensen, Kim B.
通讯作者：
Jensen, Kim B.
影响因子：
6.5
作者：
Janson, David G.;Saintigny, Gaelle;El Ghalbzouri, Abdoelwaheb
通讯作者：
El Ghalbzouri, Abdoelwaheb
DOI：
10.1242/dev.012047
发表时间：
2007-12
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Robertson EJ;Charatsi I;Joyner CJ;Koonce CH;Morgan M;Islam A;Paterson C;Lejsek E;Arnold SJ;Kallies A;Nutt SL;Bikoff EK
通讯作者：
Bikoff EK
影响因子：
5.9
作者：
Gomez, Celine;Chua, Wesley;Miremadi, Ahmad;Quist, Sven;Headon, Denis J.;Watt, Fiona M.
通讯作者：
Watt, Fiona M.