皮肤是保护机体免受病原体、毒性物质和其它有害物质入侵的第一道屏障,它在人类一生中持续不断地更新,改变其尺寸、形态以适应对机体的覆盖和保护。
成人的表皮组织由许多层构成,干细胞位于最底层,其任务就是产生新生细胞,随后分化并向上移动到特殊的皮肤层中去发挥相应的作用,分化的过程主要包括细胞特性的永久改变。皮肤必须维持干细胞和分化细胞水平的平衡,否则会导致组织结构和功能异常,然而此前人们并不清楚维持这种平衡的分子机制。
日前,研究人员发现细胞的密度和拥挤程度对单一干细胞的命运决定具有指导作用,并在组织内分化细胞的运动上扮演着关键角色,也就是说
,皮肤干细胞能感知其周围的细胞密度并作出响应的反应,从而确保所有细胞类型都能够正确定位到组织内部。
为了探究皮肤如何知道自己所处的位置并发挥作用,研究人员对胚胎小鼠组织和培养的皮肤干细胞进行分析,发现拥挤在一起所产生的局部压力会促进干细胞分化,分裂的干细胞能进一步诱导干细胞层出现一种局部的拥挤效应,诱发细胞变形;更有意思的是,细胞之间的挤压和变形能够诱发附近细胞出现分化,这种拥挤和挤压的细胞能够改变自身特性,从底层的局部压力中逃脱并不断向上运动。研究人员认为,这些细胞能够感知其附近细胞的行为变化,并以一种有效简单的方法来帮助维持组织的尺寸、结构和功能。
该研究首次阐明了人类皮肤通过简单的自我组织原则来产生并且维持其结构和功能的机制
,未来研究人员将结合计算机通信模型开发皮肤干细胞增殖的靶向调控技术,以期为某些皮肤癌症患者找到新型疗法。
推荐阅读原文:
Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification.
To establish and maintain organ structure and function, tissues need to balance stem cell proliferation and differentiation rates and coordinate cell fate with position. By quantifying and modelling tissue stress and deformation in the mammalian epidermis, we find that this balance is coordinated through local mechanical forces generated by cell division and delamination. Proliferation within the basal stem/progenitor layer, which displays features of a jammed, solid-like state, leads to crowding, thereby locally distorting cell shape and stress distribution. The resulting decrease in cortical tension and increased cell–cell adhesion trigger differentiation and subsequent delamination, reinstating basal cell layer density. After delamination, cells establish a high-tension state as they increase myosin II activity and convert to E-cadherin-dominated adhesion, thereby reinforcing the boundary between basal and suprabasal layers. Our results uncover how biomechanical signalling integrates single-cell behaviours to couple proliferation, cell fate and positioning to generate a multilayered tissue.