Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, 1 Baylor Plaza, BCM 505, Houston, TX, 77030, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, 1 Baylor Plaza, BCM 505, Houston, TX, 77030, USA.
Nat Commun. 2019 Sep 6;10(1):4042. doi: 10.1038/s41467-019-11880-9.
Tissue injury induces changes in cellular identity, but the underlying molecular mechanisms remain obscure. Here, we show that upon damage in a mouse model, epidermal cells at the wound edge convert to an embryonic-like state, altering particularly the cytoskeletal/extracellular matrix (ECM) components and differentiation program. We show that SOX11 and its closest relative SOX4 dictate embryonic epidermal state, regulating genes involved in epidermal development as well as cytoskeletal/ECM organization. Correspondingly, postnatal induction of SOX11 represses epidermal terminal differentiation while deficiency of Sox11 and Sox4 accelerates differentiation and dramatically impairs cell motility and re-epithelialization. Amongst the embryonic genes reactivated at the wound edge, we identify fascin actin-bundling protein 1 (FSCN1) as a critical direct target of SOX11 and SOX4 regulating cell migration. Our study identifies the reactivated embryonic gene program during wound repair and demonstrates that SOX11 and SOX4 play a central role in this process.
组织损伤会引起细胞身份的变化，但潜在的分子机制仍不清楚。在这里，我们表明在小鼠模型的损伤后，伤口边缘的表皮细胞转变为类似胚胎的状态，特别是改变细胞骨架/细胞外基质 (ECM) 成分和分化程序。我们表明 SOX11 及其最接近的亲属 SOX4 决定了胚胎表皮状态，调节参与表皮发育以及细胞骨架/ECM 组织的基因。相应地，SOX11 的诱导在出生后抑制表皮终末分化，而 Sox11 和 Sox4 的缺乏则加速分化，并显著损害细胞迁移和再上皮化。在伤口边缘重新激活的胚胎基因中，我们鉴定出细丝蛋白 1 (FSCN1) 作为 SOX11 和 SOX4 调节细胞迁移的关键直接靶标。我们的研究确定了伤口修复过程中重新激活的胚胎基因程序，并表明 SOX11 和 SOX4 在这个过程中发挥了核心作用。
