Adult skin fibroblast state change in murine wound healing.
Adult skin fibroblast state change in murine wound healing.
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DOI：
10.1038/s41598-022-27152-4
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发表时间：
2023-01-17
影响因子：
4.6
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中科院分区：
文献类型：
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伤口愈合是一个组织良好的动态过程，涉及协调连续的阶段：体内平衡、炎症、增殖和消退。成纤维细胞在皮肤创面愈合过程中起着重要作用，如创面收缩和生长因子的释放，而生长因子在血管生成和组织重塑中起着重要作用。在慢性伤口患者中发现了异常的成纤维细胞表型。在这项工作中，我们分析了伤口后第4天小鼠正常和受伤皮肤的scRNA-seq数据集，以研究伤口愈合增殖阶段成纤维细胞的异质性。成分分析显示，与正常皮肤（3.9%）相比，受伤皮肤中成纤维细胞的一个特定亚群（簇3）主要增加（14%）。该亚群的特征是由质膜蛋白Sfrp2 + Sfrp4 + Sfrp1 +和转录因子Ebf1 + Prrx1 + Maged1 +标记的基因特征。差异基因表达和富集分析发现，在受伤皮肤的成纤维细胞的新兴亚群中，上皮细胞向间充质细胞转化（EMT）和血管生成被上调。使用另外两个小鼠损伤皮肤的数据集证实，在损伤后第2,7和14天，簇3样成纤维细胞增加，并在第7天达到峰值。通过使用ConnectivityMap数据库中的药物特征对受伤皮肤和正常皮肤的成纤维细胞亚群的差异基因表达谱进行相似性检查，我们确定了能够模拟伤口愈合期间成纤维细胞中观察到的基因表达变化的药物。TTNPB、椎体蛋白和烟酸被确定为能够诱导伤口愈合所需的成纤维细胞基因表达谱的候选药物。另一方面，甲氨氨基酚、异环磷酰胺和戊丁醇被认为在伤口愈合过程中拮抗已鉴定的成纤维细胞差异表达谱，可能导致伤口愈合延迟。总之，对小鼠皮肤伤口愈合转录组数据集的分析表明，成纤维细胞亚群能够诱导EMT，并进一步推断可能作为诱导伤口愈合的潜在候选药物进行测试。
Wound healing is a well-organized dynamic process involving coordinated consecutive phases: homeostasis, inflammation, proliferation and resolution. Fibroblasts play major roles in skin wound healing such as in wound contraction and release of growth factors which are of importance in angiogenesis and tissue remodeling. Abnormal fibroblast phenotypes have been identified in patients with chronic wounds. In this work, we analyzed scRNA-seq datasets of normal and wounded skin from mice at day 4 post-wound to investigate fibroblast heterogeneity during the proliferative phase of wound healing. Compositional analysis revealed a specific subset of fibroblast (cluster 3) that primarily increased in wounded skin (14%) compared to normal skin (3.9%). This subset was characterized by a gene signature marked by the plasma membrane proteins Sfrp2 + Sfrp4 + Sfrp1 + and the transcription factors Ebf1 + Prrx1 + Maged1 + . Differential gene expression and enrichment analysis identified epithelial to mesenchymal transition (EMT) and angiogenesis to be upregulated in the emerging subset of fibroblasts of the wounded skin. Using two other datasets for murine wounded skin confirmed the increase in cluster 3-like fibroblasts at days 2, 7 and 14 post-wounding with a peak at day 7. By performing a similarity check between the differential gene expression profile between wounded and normal skin for this emerging fibroblast subset with drug signature from the ConnectivityMap database, we identified drugs capable of mimicking the observed gene expression change in fibroblasts during wound healing. TTNPB, verteprofin and nicotinic acid were identified as candidate drugs capable of inducing fibroblast gene expression profile necessary for wound healing. On the other hand, methocarbamol, ifosfamide and penbutolol were recognized to antagonize the identified fibroblast differential expression profile during wound healing which might cause delay in wound healing. Taken together, analysis of murine transcriptomic skin wound healing datasets suggested a subset of fibroblasts capable of inducing EMT and further inferred drugs that might be tested as potential candidates to induce wound closure.
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DOI：
10.1002/dvdy.24561
发表时间：
2018-03
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Haensel D;Dai X
通讯作者：
Dai X
影响因子：
6.6
作者：
Abouhashem, Ahmed S.;Singh, Kanhaiya;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
DOI：
10.1111/wrr.12205
发表时间：
2014-09
期刊：
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子：
--
作者：
Barrientos S;Brem H;Stojadinovic O;Tomic-Canic M
通讯作者：
Tomic-Canic M
影响因子：
2.6
作者：
Gosain, A;Luisa, MD;DiPietro, A
通讯作者：
DiPietro, A
DOI：
10.1161/atvbaha.111.241836
发表时间：
2012-03
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Digby JE;Martinez F;Jefferson A;Ruparelia N;Chai J;Wamil M;Greaves DR;Choudhury RP
通讯作者：
Choudhury RP