Homeostasis and function of limbal epithelial stem cells (LESCs) rely on the limbal niche, which, if dysfunctional, leads to limbal epithelial stem cell deficiency (LSCD) and impaired vision. Hence, recovery of niche function is a principal therapeutic goal in LSCD, but the molecular mechanisms of limbal niche homeostasis are still largely unknown. Here, we report that the neural crest transcription factor SOX10, which is expressed in neural crest‐derived limbal niche cells (LNCs), is required for LNCs to promote survival of LESCs both in vivo and in vitro. In fact, using mice with a Sox10 mutation and in vitro coculture experiments, we show that SOX10 in LNCs stimulates the production of KIT ligand (KITL), which in turn activates in LESCs the KIT‐AKT signalling pathway that protects the cells against activated CASPASE 3‐associated cell death. These results suggest that SOX10 and the KITL/KIT‐AKT pathway play key roles in limbal niche homeostasis and LESC survival. These findings provide molecular insights into limbal niche function and may point to rational approaches for therapeutic interventions in LSCD.

中文翻译：

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在SOX10的控制下，角膜缘生壁细胞产生的KIT配体通过激活KIT / AKT信号通路来维持角膜缘上皮干细胞存活。

角膜缘上皮干细胞（LESC）的稳态和功能依赖于角膜缘生境，如果功能失调，则会导致角膜缘上皮干细胞缺乏症（LSCD）和视力受损。因此，恢复小生境功能是LSCD的主要治疗目标，但是边缘小生境稳态的分子机制仍是未知之数。在这里，我们报道了神经c转录因子SOX10在神经c衍生的角膜缘利基细胞（LNCs）中表达，是LNC在体内和体外促进LESC存活所必需的。实际上，使用带有Sox10的小鼠突变和体外共培养实验，我们发现LNC中的SOX10刺激了KIT配体（KITL）的产生，而KIT配体又在LESC中激活了KIT-AKT信号通路，从而保护细胞免受激活的CASPASE 3相关的细胞死亡。这些结果表明，SOX10和KITL / KIT‐AKT途径在角膜缘生境稳态和LESC存活中起关键作用。这些发现提供了对角膜缘利基功能的分子见解，并可能为LSCD的治疗干预提供了合理的方法。