Pax7 Expressing Cells Contribute to Dermal Wound Repair, Regulating Scar Size through a β-Catenin Mediated Process
Pax7 Expressing Cells Contribute to Dermal Wound Repair, Regulating Scar Size through a β-Catenin Mediated Process
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DOI：
10.1002/stem.688
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发表时间：
2011-09-01
期刊：
影响因子：
5.2
通讯作者：
Alman, Benjamin A.
中科院分区：
文献类型：
--
作者：
Amini-Nik, Saeid;Glancy, Dylan;Alman, Benjamin A.
在皮肤伤口愈合过程中，成纤维细胞样细胞重建修复皮肤的真皮隔室，填充伤口间隙。这些细胞中的一部分在修复过程的增殖阶段具有β -连环蛋白/ t细胞因子（TCF）信号的转录活性，β -连环蛋白水平通过调节真皮成纤维细胞的数量来控制最终形成的疤痕的大小。在这里，我们进行了细胞谱系研究，以揭示在伤口修复过程中激活β -连环蛋白信号的真皮细胞来源。使用报告小鼠，我们发现在早期伤口中，tcf依赖性转录被激活的细胞表达参与肌肉发育的基因。我们使用永久标记表达Pax7（肌肉祖细胞）或Mck（分化肌细胞）的细胞的小鼠，发现愈合伤口中有四分之一的真皮细胞是表达Pax7的后代，但没有Mck的后代。在Pax7表达的后代中去除一个β -catenin等位基因会导致疤痕大小明显减小，并且参与伤口修复的Pax7表达的后代细胞减少。在伤口愈合过程中，β -连环蛋白激活导致肌肉卫星细胞呈纤维化表型，这是修复过程中真皮细胞的来源。干细胞2011；29:1371 - 1379
During skin wound healing, fibroblast-like cells reconstitute the dermal compartment of the repaired skin filling the wound gap. A subset of these cells are transcriptionally active for beta-catenin/T-cell factor (TCF) signaling during the proliferative phase of the repair process, and beta-catenin levels control the size of the scar that ultimately forms by regulating the number of dermal fibroblasts. Here, we performed cell lineage studies to reveal a source of the dermal cells in which beta-catenin signaling is activated during wound repair. Using a reporter mouse, we found that cells in the early wound in which TCF-dependent transcription is activated express genes involved in muscle development. Using mice in which cells express Pax7 (muscle progenitors) or Mck (differentiated myocytes) are permanently labeled, we showed that one quarter of dermal cells in the healing wound are Pax7 expressing progeny, but none are Mck progeny. Removing one allele of beta-catenin in Pax7 expressing progeny resulted in a significantly smaller scar size with fewer Pax7 expressing progeny cell contributing to wound repair. During wound healing, beta-catenin activation causes muscle satellite cells to adopt a fibrotic phenotype and this is a source of dermal cells in the repair process. STEM CELLS 2011;29:1371-1379