拉伸响应性成纤维细胞程序在皮肤扩张过程中促进表皮干细胞自我更新
A stretch-responsive fibroblast program promotes epidermal stem cell self-renewal during skin expansion.
摘要(中文译文)
牵张介导的组织扩张常用于重建外科手术中以生长额外皮肤。为确保协调生长，两个主要的皮肤 compartments——表皮和真皮——必须协同扩张。成纤维细胞如何响应牵张介导的组织扩张以支持角质形成细胞增殖，目前尚不清楚。在此，我们绘制了体内成纤维细胞对牵张的转录响应图谱，并证明牵张力促使成纤维细胞退出静息状态并重新启动增殖。同时，成纤维细胞减少胶原蛋白产生并上调细胞外基质重塑因子，采用更接近胚胎期的程序。由于胚胎成纤维细胞广泛用作饲养层以支持表皮干细胞扩增用于临床应用，我们利用该模型表明低胶原状态增强表皮干细胞自我更新，从而在皮肤扩张过程中协调表皮和真皮响应。这些发现为指导体内牵张介导的组织扩张方案设计以及用于临床应用的体外皮肤移植物生产提供了宝贵见解。
Abstract
Stretch-mediated tissue expansion is commonly used to grow extra skin for reconstructive surgeries. To ensure harmonious growth, the two main skin compartments, the epidermis and the dermis, must both expand in a coordinated manner. How fibroblasts respond to stretch-mediated tissue expansion in supporting keratinocyte proliferation remains unclear. Here we map the fibroblast transcriptional response to stretching in vivo and demonstrate that stretching forces fibroblasts to exit their quiescent state and restart proliferation. Concurrently, fibroblasts reduce collagen production and upregulate extracellular matrix remodelling factors, adopting a more embryonic-like program. Because embryonic fibroblasts are widely used as feeder layers to support the expansion of epidermal stem cells for clinical application, we leveraged this model to show that a low collagen state enhances epidermal stem cell self-renewal, thereby coordinating epidermal and dermal responses during skin expansion. These findings provide valuable insights to guide the design of in vivo stretch-mediated tissue expansion protocols and the production of in vitro skin grafts for clinical application.
如何引用
AMA
Caroline Aguilera Stewart, Ceyhun Alar, Gaia Andrea Gozza, Leslie Bargsted, Ioanna Kaklamanou, Maria Pia Polito, et al. A stretch-responsive fibroblast program promotes epidermal stem cell self-renewal during skin expansion.. Nature communications. 2026; doi:10.1038/s41467-026-73979-0.
APA
Caroline Aguilera Stewart, Ceyhun Alar, Gaia Andrea Gozza, Leslie Bargsted, Ioanna Kaklamanou, Maria Pia Polito, et al (2026). A stretch-responsive fibroblast program promotes epidermal stem cell self-renewal during skin expansion.. Nature communications. https://doi.org/10.1038/s41467-026-73979-0
GB/T 7714
Caroline Aguilera Stewart, Ceyhun Alar, Gaia Andrea Gozza, Leslie Bargsted, Ioanna Kaklamanou, Maria Pia Polito, et al. A stretch-responsive fibroblast program promotes epidermal stem cell self-renewal during skin expansion.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73979-0.
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