Cytokines Induce Monkey Neural Stem Cell Differentiation through Notch Signaling

• Published in: BioMed research international Vol. 2020; no. 2020; pp. 1 - 13
• Main Authors: Lu, Lixia, Tian, Haibin, Zhang, Ying, Liu, Yuehua, Zhang, Ce, Gao, Zhengliang, Han, Xin-Xin, Cai, Chunhui, Xie, Xiaoyun, Pan, Jie, Ren, Jie, He, Hua, Zhu, Lu-Ying, Yu, Liming, Wang, Min, Chen, Li
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2020; Hindawi; Hindawi Limited
• Subjects: Animals; Antibodies; Bone morphogenetic protein 4; Bone Morphogenetic Protein 4 - pharmacology; Brain; Brain - cytology; Brain damage; Brain injury; Brain research; Cell cycle; Cell differentiation; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Central nervous system; Colforsin - pharmacology; Cytokines; Cytokines - pharmacology; Differentiation (biology); Epidermal growth factor; Forskolin; Injuries; Kinases; Leukemia; Leukemia inhibitory factor; Leukemia Inhibitory Factor - pharmacology; Macaca fascicularis; Male; Medical research; Monkeys; Morphology; Nervous system; Neural cell transplants; Neural stem cells; Neural Stem Cells - drug effects; Neurogenesis - drug effects; Pluripotency; Primates; Receptors, Notch - metabolism; Regenerative medicine; Retinoic acid; Signal Transduction - drug effects; Signaling; Spinal cord injuries; Stem cell transplantation; Stem cells; Transplantation; Tretinoin - pharmacology
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2020/1308526

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.