Defining compartmentalized stem cell populations with distinct cell division dynamics in the ocular surface epithelium.
Defining compartmentalized stem cell populations with distinct cell division dynamics in the ocular surface epithelium.
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DOI：
10.1242/dev.197590
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发表时间：
2020-12-16
期刊：
影响因子：
--
通讯作者：
Sada A
中科院分区：
文献类型：
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作者：
Ishii R;Yanagisawa H;Sada A
成人组织含有标记保留细胞（LRC），其相对较慢的循环，被认为代表组织干细胞（SC）的特性。在眼表上皮中，LRC存在于利姆布斯和结膜穹窿中;然而，由于缺乏适当的分子标记物，这些LRC的特征仍不清楚。使用三个CreER转基因小鼠系，我们表明，眼表上皮细胞容纳空间上不同的人口与不同的细胞分裂动力学。在利姆布斯，长寿命的Slc 1a 3 CreER标记的干细胞要么向中央角膜迁移，要么在角膜缘区域内缓慢地横向扩展它们的克隆。在中央角膜中，用Dlx 1CreER和K14 CreER标记的非LRC表现为短寿命祖细胞。球结膜上皮，穹窿和睑室再生的区域独特的SC群体。严重的角膜损伤导致SC隔室和结膜化的取消，而轻度的角膜缘损伤诱导利姆布斯中侧向扩张克隆的快速增加。总之，我们的工作定义了小鼠眼内稳态的区室化多个SC/祖细胞群体及其对损伤的反应行为变化。总结：这项研究提供了遗传工具，以精确地标记和检查的动态行为的异质干细胞群体在眼表上皮。
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 Slc1a3CreER-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 Dlx1CreER and K14CreER 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. Summary: This study provides genetic tools to precisely mark and examine the dynamic behavior of heterogeneous stem cell populations in the ocular surface epithelium.