Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Stem Cell Reports. 2022 Oct 11;17(10):2334-2348. doi: 10.1016/j.stemcr.2022.08.011. Epub 2022 Sep 22.
After injury, a cascade of events repairs the damaged tissue, including expansion and differentiation of the progenitor pool and redeposition of matrix. To guide future wound regeneration strategies, we compared single-cell sequencing of regenerative (third phalangeal element [P3]) and fibrotic (second phalangeal element [P2]) digit tip amputation (DTA) models as well as traumatic heterotopic ossification (HO; aberrant). Analyses point to a common initial response to injury, including expansion of progenitors, redeposition of matrix, and activation of transforming growth factor β (TGF-β) and WNT pathways. Surprisingly, fibrotic P2 DTA showed greater transcriptional similarity to HO than to regenerative P3 DTA, suggesting that gene expression more strongly correlates with healing outcome than with injury type or cell origin. Differential analysis and immunostaining revealed altered activation of inflammatory pathways, such as the complement pathway, in the progenitor cells. These data suggests that common pathways are activated in response to damage but are fine tuned within each injury. Modulating these pathways may shift the balance toward regenerative outcomes.
损伤后，一系列事件修复受损组织，包括祖细胞库的扩增和分化以及基质的再沉积。为了指导未来的伤口再生策略，我们比较了再生（第三指节元素 [P3]）和纤维化（第二指节元素 [P2]）指尖切断（DTA）模型以及创伤性异位骨化（HO；异常）的单细胞测序。分析表明，损伤后存在共同的初始反应，包括祖细胞的扩增、基质的再沉积以及转化生长因子 β（TGF-β）和 WNT 途径的激活。令人惊讶的是，纤维化的 P2 DTA 与 HO 的转录相似性大于与再生的 P3 DTA，这表明基因表达与愈合结果的相关性强于与损伤类型或细胞起源的相关性。差异分析和免疫染色显示，祖细胞中炎症途径（如补体途径）的激活发生改变。这些数据表明，共同途径在损伤后被激活，但在每个损伤中都被精细调节。调节这些途径可能会使平衡向再生结果倾斜。
