Regionally-Specified Second Trimester Fetal Neural Stem Cells Reveals Differential Neurogenic Programming

Neural stem/progenitor cells (NSC) have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ) of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS) when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6%) over other sources (range of 0%–27.5%, p神经干/祖细胞（Neural stem/progenitor cells, NSC）具备治疗多种神经系统疾病的潜力，例如帕金森病（Parkinson Disease）与多发性硬化（multiple sclerosis）。目前，科研人员仅能从成体大脑的海马体（hippocampus）和室下区（subventricular zone, SVZ）中分离出NSC。目前尚不清楚在孕中期中枢神经系统（central nervous system, CNS）经历大规模重塑与生长的阶段，NSC是否广泛分布于其所有区域。研究人员可从孕中期的大脑、丘脑、室下区、海马体、丘脑、小脑、脑干以及脊髓中分离得到多能性NSC，并将其培养为克隆神经球（clonal neurospheres），且其增殖频率随妊娠时长增加而升高。此类NSC可在体外（in vitro）与体内（in vivo）环境中完成多谱系分化，且可在发育中小鼠模型中实现定植。不同区域来源的NSC具有不同的表型特征，其中海马体来源的NSC展现出显著更高的神经发生潜能（53.6%），高于其他来源的NSC（神经发生潜能范围为0%~27.5%，p