CXCR4 activation promotes differentiation of human embryonic stem cells to neural stem cells.
G protein-coupled receptors (GPCRs) are involved in many fundamental cellular responses such as growth, death, movement, transcription and excitation. Their roles in human stem cell neural specialization are not well understood. In this study, we aimed to identify GPCRs that may play a role in the differentiation of human embryonic stem cells (hESCs) to neural stem cells (NSCs). Using a feeder-free hESC neural differentiation protocol, we found that the expression of several chemokine receptors changed dramatically during the hESC/NSC transition. Especially, the expression of CXCR4 increased approximately 50 folds in NSCs compared to the original hESCs. CXCR4 agonist SDF-1 promoted, whereas the antagonist AMD3100 delayed the neural induction process. In consistence with antagonizing CXCR4, knockdown of CXCR4 in hESCs also blocked the neural induction and cells with reduced CXCR4 were rarely positive for Nestin and Sox1-staining. Taken together, our results suggest that CXCR4 is involved in the neural induction process of hESC and it might be considered as a target to facilitate NSC production from hESCs in regenerative medicine.
Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Lijun
L
Zhang
Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Qiuhong
Q
Hua
Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Kaiyi
K
Tang
Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Changjie
C
Shi
Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: xxie@simm.ac.cn.
Xin
X
Xie
Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: ru.zhang@tongji.edu.cn.
Ru
R
Zhang
D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
C527276:CXCR4 protein, human; D064231:Nestin; D019718:Receptors, CXCR4
CXCR4; SDF-1; chemokine receptor; human embryonic stem cell; neural differentiation; neural stem/precursor cell