Cytokines Induce Monkey Neural Stem Cell Differentiation through Notch Signaling.
Min WangLi-Ming YuLu-Ying ZhuHua HeJie RenJie PanXiaoyun XieChunhui CaiLixia LvHaibin TianLi ChenYing ZhangYue-Hua LiuCe ZhangZhengliang GaoXin-Xin HanPublished in: BioMed research international (2020)
The mammalian central nervous system (CNS) has a limited ability to renew the damaged cells after a brain or spinal cord injury whether it is nonhuman primates like monkeys or humans. Transplantation of neural stem cells (NSCs) is a potential therapy for CNS injuries due to their pluripotency and differentiation abilities. Cytokines play an important role in CNS development and repair of CNS injuries. However, the detailed cytokine signaling response in monkey neural stem cells is rarely studied. In our previous research, we isolated NSCs from the adult monkey brain and found the effects of cytokines on monkey NSCs. Now, we further analyzed the regulation mechanisms of cytokines to the proliferation of monkey NSCs such as bone morphogenic protein 4 (BMP4), BMP4/leukaemia inhibitory factor (LIF), or retinoic acid (RA)/Forskolin. The data showed that BMP4 inhibited cell proliferation to arrest, but it did not affect the stemness of NSCs. BMP4/LIF promoted the astrocyte-like differentiation of monkey NSCs, and RA/forskolin induced the neuronal differentiation of monkey NSCs. BMP4/LIF and RA/forskolin induced monkey NSC differentiation by regulating Notch signaling. These results provide some theoretical evidence for NSC therapy to brain or spinal cord injury in regenerative medicine.
Keyphrases
- spinal cord injury
- neural stem cells
- mesenchymal stem cells
- stem cells
- bone regeneration
- cell proliferation
- blood brain barrier
- resting state
- diabetic rats
- epithelial mesenchymal transition
- signaling pathway
- machine learning
- electronic health record
- systemic lupus erythematosus
- climate change
- artificial intelligence
- brain injury
- bone loss
- systemic sclerosis
- amino acid
- postmenopausal women