法国巴黎大学Philippos Mourikis、Frederic Relaix等研究人员合作发现，组织损伤诱导一种保守的应激反应来启动静态肌肉干细胞活化。2021年2月19日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员表示，细胞可塑性是响应各种脊椎动物器官损伤的基本特性。组织损伤能够触发干细胞/祖细胞的活化和增殖，从而恢复体内平衡，例如在骨骼、皮肤和骨骼肌中。分化的细胞也可以被激活，并在去分化后最终增殖，如肝切除术后的肝细胞或新生小鼠心肌细胞。但是，当细胞损伤不可逆时，也可以激发细胞死亡途径。揭示细胞退出体内稳态时的早期转录途径对于理解其特性和开发用于实验操作的工具至关重要。然而，尽管进行了广泛的研究，但对于在体内发生的组织损伤的早期，细胞类型特异性或保守反应的程度、动力学和性质仍然不清楚。

研究人员从完整、分离和受伤的肌肉和肝脏生成了单细胞和细胞核图谱，并确定了这些器官中多种细胞类型共有的常见应激反应特征。研究人员在广泛组织范围内的发表数据集中检测到了这种普遍的应激反应，这表明它具有很高的保守性，但在单细胞参考图谱中也显示出很大程度的数据失真。使用静止的肌肉干细胞作为损伤后细胞活化的范例，研究人员捕获了肌肉损伤后的早期细胞活化，发现必需的ERK1/2初级增殖信号先于Notch调控的成肌程序启动。这项研究定义了响应于组织扰动的初始事件，并确定了与细胞特异性适应性改变并行起作用的保守转录应激反应。 

附：英文原文

Title: Tissue damage induces a conserved stress response that initiates quiescent muscle stem cell activation

Author: Léo Machado, Perla Geara, Jordi Camps, Matthieu Dos Santos, Fatima Teixeira-Clerc, Jens Van Herck, Hugo Varet, Rachel Legendre, Jean-Michel Pawlotsky, Maurilio Sampaolesi, Thierry Voet, Pascal Maire, Frederic Relaix, Philippos Mourikis

Issue&Volume: 2021-02-19

Abstract: Tissue damage dramatically alters how cells interact with their microenvironment.These changes in turn dictate cellular responses, such as stem cell activation, yetearly cellular responses in vivo remain ill defined. We generated single-cell and nucleus atlases from intact, dissociated,and injured muscle and liver and identified a common stress response signature sharedby multiple cell types across these organs. This prevalent stress response was detectedin published datasets across a range of tissues, demonstrating high conservation butalso a significant degree of data distortion in single-cell reference atlases. Usingquiescent muscle stem cells as a paradigm of cell activation following injury, wecaptured early cell activation following muscle injury and found that an essentialERK1/2 primary proliferation signal precedes initiation of the Notch-regulated myogenicprogram. This study defines initial events in response to tissue perturbation andidentifies a broadly conserved transcriptional stress response that acts in parallelwith cell-specific adaptive alterations.

DOI: 10.1016/j.stem.2021.01.017

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00017-5