Open AccessKIT ligand produced by limbal niche cells under control of SOX10 maintains limbal epithelial stem cell survival by activating the KIT/AKT signalling pathway
Author(s) -
Su Zhongyuan,
Wang Jing,
Lai Qinghua,
Zhao Huanyu,
Hou Ling
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15830
Subject(s) - sox10 , biology , microbiology and biotechnology , stem cell , protein kinase b , limbal stem cell , niche , stem cell factor , transcription factor , neural crest , cancer research , signal transduction , immunology , corneal epithelium , progenitor cell , epithelium , genetics , embryo , ecology , gene
Abstract 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.