Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba 305-8577, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8577, Japan.
Development. 2020 Dec 16;147(24):dev197590. doi: 10.1242/dev.197590.
Adult tissues contain label-retaining cells (LRCs), which are relatively slow-cycling and considered to represent a property of tissue stem cells (SCs). In the ocular surface epithelium, LRCs are present in the limbus and conjunctival fornix; however, the character of these LRCs remains unclear, owing to lack of appropriate molecular markers. Using three CreER transgenic mouse lines, we demonstrate that the ocular surface epithelium accommodates spatially distinct populations with different cell division dynamics. In the limbus, long-lived Slc1a3-labeled SCs either migrate centripetally toward the central cornea or slowly expand their clones laterally within the limbal region. In the central cornea, non-LRCs labeled with Dlx1 and K14 behave as short-lived progenitor cells. The conjunctival epithelium in the bulbar, fornix and palpebral compartment is regenerated by regionally unique SC populations. Severe damage to the cornea leads to the cancellation of SC compartments and conjunctivalization, whereas milder limbal injury induces a rapid increase of laterally expanding clones in the limbus. Taken together, our work defines compartmentalized multiple SC/progenitor populations of the mouse eye in homeostasis and their behavioral changes in response to injury.
成人组织中含有标记保留细胞（LRCs），这些细胞增殖缓慢，被认为代表组织干细胞（SCs）的特性。在眼表面上皮中，LRCs 存在于角膜缘和结膜穹窿；然而，由于缺乏适当的分子标记物，这些 LRCs 的特性仍不清楚。我们使用三种 CreER 转基因小鼠系证明，眼表面上皮容纳具有不同细胞分裂动力学的空间上不同的群体。在角膜缘，长寿命的 Slc1a3 标记的SCs 要么向中央角膜中心迁移，要么在角膜缘区域内缓慢地侧向扩展其克隆。在中央角膜中，用 Dlx1 和 K14 标记的非 LRCs 表现为短寿命祖细胞。球部、穹窿和睑部的结膜上皮由区域特有的 SC 群体再生。角膜的严重损伤导致 SC 隔室和结膜化的取消，而较轻的角膜缘损伤诱导角膜缘中侧向扩展克隆的快速增加。总之，我们的工作定义了小鼠眼睛中处于静止状态的分区化的多个 SC/祖细胞群体及其对损伤的反应的行为变化。
