Ferrodifferentiation regulates neurodevelopment via ROS generation  

作　　者：Shiyang Chang Peina Wang Yingying Han Qiang Ma Zeyuan Liu Suijuan Zhong Yufeng Lu Ruiguo Chen Le Sun Qian Wu Guofen Gao Xiaoqun Wang Yan-Zhong Chang 

机构地区：[1]Laboratory of Molecular Iron Metabolism,Ministry of Education Key Laboratory of Molecular and Cellular Biology,Hebei Key Laboratory of Animal Physiology,Biochemistry,and Molecular Biology,College of Life Sciences,Hebei Normal University,Shijiazhuang 050024,China [2]College of Basic Medicine,Hebei Medical University,Shijiazhuang 050017,China [3]State Key Laboratory of Brain and Cognitive Science,CAS Center for Excellence in Brain Science and Intelligence Technology(Shanghai),Institute of Biophysics,Chinese Academy of Sciences(CAS),BNU IDG/McGovern Institute for Brain Research,Beijing 100101,China [4]State Key Laboratory of Cognitive Neuroscience and Learning,Beijing Normal University,Beijing 100875,China [5]Beijing Institute of Brain Disorders,Laboratory of Brain Disorders,Ministry of Science and Technology,Collaborative Innovation Center for Brain Disorders,Capital Medical University,Beijing 100069,China

出　　处：《Science China(Life Sciences)》2023年第8期1841-1857,共17页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(30871260);the Natural Science Foundation of Hebei Province(E2021205003,C2019206575);the Science and Technology Project of Hebei Education Department(QN2019005,BJK2022049)。

摘　　要：Iron is important for life,and iron deficiency impairs development,but whether the iron level regulates neural differentiation remains elusive.In this study,with iron-regulatory proteins(IRPs)knockout embryonic stem cells(ESCs)that showed severe iron deficiency,we found that the Pax6-and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1^(-/-)IRP2^(-/-)ESCs were significantly decreased after inducing neural differentiation.Consistently,in vivo study showed that the knockdown of IRP1 in IRP2^(-/-)fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons.These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation.When supplementing IRP1^(-/-)IRP2^(-/-)ESCs with iron,these ESCs could differentiate normally.Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species(ROS)production caused by the substantially low level of iron and the downregulation of iron-sulfur cluster protein ISCU,which,in turn,affected the proliferation and differentiation of stem cells.Thus,the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation.

关 键 词：IRPs ESCS IRON DIFFERENTIATION NEURODEVELOPMENT ROS 

分 类 号：Q42[生物学—神经生物学]