小柯机器人

2022年1月24日，《细胞—干细胞》杂志在线发表了美国科学家的一项最新研究成果。来自斯坦福大学医学院的Michael T. Longaker、Geoffrey C. Gurtner等研究人员合作揭示瘢痕形成和再生伤口愈合中的不同分子事件。

研究人员报告了驱动皮肤伤口细胞走向疤痕或再生命运的不同分子事件。研究人员在转录（单细胞RNA测序）、蛋白质（TIMSTOF蛋白质组学）和组织（细胞外基质超微结构分析）水平上对瘢痕与YAP抑制诱导的伤口再生进行分析。利用细胞表面条码，研究人员整合了这些数据，揭示了纤维化和再生的愈合"分子轨迹"。结果表明，破坏YAP的机械传导，可以通过激活Trps1和Wnt信号的成纤维细胞产生再生修复。最后，通过体内基因敲除和在伤口中过量表达，研究人员确定Trps1是一个关键的调节基因，对伤口再生是必要的，也是部分充分的。这些发现可作为伤口再生的多组学图谱，并可能对病理性纤维化有治疗意义。

据了解，再生是组织修复的圣杯，但皮肤损伤通常会产生纤维化的、无功能的疤痕。开发促进再生的疗法需要严格了解从损伤到纤维化或再生的分子进展。

附：英文原文

Title: Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing

Author: Shamik Mascharak, Heather E. Talbott, Michael Januszyk, Michelle Griffin, Kellen Chen, Michael F. Davitt, Janos Demeter, Dominic Henn, Clark A. Bonham, Deshka S. Foster, Nancie Mooney, Ran Cheng, Peter K. Jackson, Derrick C. Wan, Geoffrey C. Gurtner, Michael T. Longaker

Issue&Volume: 2022-01-24

Abstract: Regeneration is the holy grail of tissue repair, but skin injury typically yieldsfibrotic, non-functional scars. Developing pro-regenerative therapies requires rigorousunderstanding of the molecular progression from injury to fibrosis or regeneration.Here, we report the divergent molecular events driving skin wound cells toward scarringor regenerative fates. We profile scarring versus YAP-inhibition-induced wound regenerationat the transcriptional (single-cell RNA sequencing), protein (timsTOF proteomics),and tissue (extracellular matrix ultrastructural analysis) levels. Using cell-surfacebarcoding, we integrate these data to reveal fibrotic and regenerative “moleculartrajectories” of healing. We show that disrupting YAP mechanotransduction yields regenerativerepair by fibroblasts with activated Trps1 and Wnt signaling. Finally, via in vivo gene knockdown and overexpression in wounds, we identify Trps1 as a key regulatorygene that is necessary and partially sufficient for wound regeneration. Our findingsserve as a multi-omic map of wound regeneration and could have therapeutic implicationsfor pathologic fibroses.

DOI: 10.1016/j.stem.2021.12.011

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00525-7

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
官方网址：https://www.cell.com/cell-stem-cell/home
投稿链接：https://www.editorialmanager.com/cell-stem-cell/default.aspx