The Protective Role of Symmetric Stem Cell Division on the Accumulation of Heritable Damage

Stem cell divisions are either asymmetric—in which one daughter cell remains a stem cell and one does not—or symmetric, in which both daughter cells adopt the same fate, either stem or non-stem. Recent studies show that in many tissues operating under homeostatic conditions stem cell division patterns are strongly biased toward the symmetric outcome, raising the question of whether symmetry confers some benefit. Here, we show that symmetry, via extinction of damaged stem-cell clones, reduces the lifetime risk of accumulating phenotypically silent heritable damage (mutations or aberrant epigenetic changes) in individual stem cells. This effect is greatest in rapidly cycling tissues subject to accelerating rates of damage accumulation over time, a scenario that describes the progression of many cancers. A decrease in the rate of cellular damage accumulation may be an important factor favoring symmetric patterns of stem cell division.干细胞分裂可分为两类：不对称分裂——即一个子代细胞保留干细胞身份，另一个则丧失干细胞特性；以及对称分裂——即两个子代细胞具有完全一致的细胞命运，要么均为干细胞，要么均为非干细胞。近期研究显示，在诸多处于稳态的组织中，干细胞的分裂模式强烈偏向对称分裂，这引发了一个核心疑问：对称分裂是否能赋予某种功能性益处？本研究证实，对称分裂可通过清除受损的干细胞克隆，降低单个干细胞在生命周期中积累表型沉默型可遗传损伤（突变或异常表观遗传修饰）的终生风险。该效应在增殖速率快、损伤积累速率随时间持续加快的组织中最为显著，而这一场景恰恰对应了多数癌症的发生发展进程。细胞损伤积累速率的降低，或许是推动干细胞选择对称分裂模式的关键影响因素之一。