加拿大卡尔加里大学Jeff Biernaskie小组发现，不同的调节程序控制伤口愈合过程中皮肤成纤维细胞的再生潜能。相关论文于2020年8月4日在线发表于《细胞—干细胞》。

使用互补的命运映射方法，研究人员表明毛囊间充质祖细胞对伤口修复的贡献有限。相比之下，以静止相关因子Hic1为标记的毛囊外祖细胞产生了大量的修复性成纤维细胞，并表现出功能性差异，从而介导伤口新生真皮中心的再生和周围瘢痕的形成。单细胞RNA-seq揭示了独特的上皮-间充质交流信号，从而使间充质能够再生。与scATAC-seq的整合突出显示了再生相关基因座内染色质可及性的变化。

最后，在伤口活化的成纤维细胞中，RUNX1和视黄酸信号的药理学调节或Hic1的基因缺失足以调节愈合结果，从而表明修复性成纤维细胞具有潜在但可改变的再生能力。

据介绍，真皮成纤维细胞在体内平衡过程中以及对损伤的反应中表现出相当大的异质性。定义修复性成纤维细胞的谱系起源以及驱动纤维化或相反地促进再生的调控程序，对于改善愈合结果至关重要。

附：英文原文

Title: Distinct Regulatory Programs Control the Latent Regenerative Potential of Dermal Fibroblasts during Wound Healing

Author: Sepideh Abbasi, Sarthak Sinha, Elodie Labit, Nicole L. Rosin, Grace Yoon, Waleed Rahmani, Arzina Jaffer, Nilesh Sharma, Andrew Hagner, Prajay Shah, Rohit Arora, Jessica Yoon, Anowara Islam, Aya Uchida, Chih Kai Chang, Jo Anne Stratton, R. Wilder Scott, Fabio M.V. Rossi, T. Michael Underhill, Jeff Biernaskie

Issue&Volume: 2020-08-04

Abstract: Dermal fibroblasts exhibit considerable heterogeneity during homeostasis and in responseto injury. Defining lineage origins of reparative fibroblasts and regulatory programsthat drive fibrosis or, conversely, promote regeneration will be essential for improvinghealing outcomes. Using complementary fate-mapping approaches, we show that hair folliclemesenchymal progenitors make limited contributions to wound repair. In contrast, extrafollicularprogenitors marked by the quiescence-associated factor Hic1 generated the bulk ofreparative fibroblasts and exhibited functional divergence, mediating regenerationin the center of the wound neodermis and scar formation in the periphery. Single-cellRNA-seq revealed unique transcriptional, regulatory, and epithelial-mesenchymal crosstalksignatures that enabled mesenchymal competence for regeneration. Integration withscATAC-seq highlighted changes in chromatin accessibility within regeneration-associatedloci. Finally, pharmacological modulation of RUNX1 and retinoic acid signaling orgenetic deletion of Hic1 within wound-activated fibroblasts was sufficient to modulatehealing outcomes, suggesting that reparative fibroblasts have latent but modifiableregenerative capacity.

DOI: 10.1016/j.stem.2020.07.008

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30346-5