Abstract：
Transit-amplifying (TA) cells are progenitors that undergo an amplification phase followed by transition into an extinction phase. A long postulated epidermal TA progenitor with biphasic behavior has not yet been experimentally observed in vivo. Here, we identify such a TA population using clonal analysis of Aspm-CreER genetic cell-marking in mice, which uncovers contribution to both homeostasis and injury repair of adult skin. This TA population is more frequently dividing than a Dlx1-CreER-marked long-term self-renewing (e.g. stem cell) population. Newly developed generalized birth-death modeling of long-term lineage tracing data shows that both TA progenitors and stem cells display neutral competition, but only the stem cells display neutral drift. The quantitative evolution of a nascent TA cell and its direct descendants shows that TA progenitors indeed amplify the basal layer before transition and that the homeostatic TA population is mostly in extinction phase. This model will be broadly useful for analyzing progenitors whose behavior changes with their clone age. This work identifies a long-missing class of non-self-renewing biphasic epidermal TA progenitors and has broad implications for understanding tissue renewal mechanisms.
摘要：
转运扩增(TA)细胞是经历扩增阶段然后转变为消光阶段的祖细胞。尚未在体内实验观察到具有双相行为的长期假定的表皮TA祖细胞。这里,我们使用小鼠Aspm-CreER遗传细胞标记的克隆分析来鉴定这样的TA群体，揭示了对成人皮肤稳态和损伤修复的贡献。该TA群体比Dlx1-CreER标记的长期自我更新(例如干细胞)群体更频繁地分裂。新开发的长期谱系追踪数据的广义出生-死亡模型表明，TA祖细胞和干细胞均表现出中性竞争，但只有干细胞显示中性漂移。新生TA细胞及其直接后代的定量进化表明，TA祖细胞确实在过渡前放大了基底层，并且稳态TA种群大多处于灭绝阶段。该模型将广泛用于分析行为随克隆年龄变化的祖细胞。这项工作确定了一类长期缺失的非自我更新双相表皮TA祖细胞，并对理解组织更新机制具有广泛意义。
