Roybon Laurent, Ma Zhi, Asztely Fredrik, Fosum Anna, Jacobsen Sten Eirik W, Brundin Patrik, Li Jia-Yi
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund, Sweden.
Stem Cells. 2006 Jun;24(6):1594-604. doi: 10.1634/stemcells.2005-0548. Epub 2006 Mar 23.
Previous studies of bone marrow-derived stem cell transdifferentiation into neurons have not involved purified cell populations and determined their exact phenotype prior to differentiation. The present study investigates whether highly purified mouse adult hematopoietic stem cells (HSCs), characterized by lineage marker depletion and expression of the cell surface markers Sca1 and c-Kit (Lin(-) Sca1(+) c-Kit(+) [LSK]), can be stimulated to adopt a neuronal fate. When the HSC(LSK) cells were cultured in vitro in neuronal differentiation medium supplemented with retinoic acid, 50% of the cells expressed the neural progenitor marker nestin and no cells had become postmitotic. Electrophysiological recordings on neuron-like cells showed that these cells were incapable of generating action potentials. When the HSC(LSK) cells either were grown in vitro together with neural precursor cells or were transplanted into the striatum or cerebellum of wild-type mouse, they either differentiated into Iba1-immunopositive macrophage/microglia or died. In conclusion, we demonstrate that adult HSC(LSK) cells do not have the capacity to leave the hematopoietic lineage and differentiate into neurons.
先前关于骨髓源性干细胞向神经元转分化的研究并未涉及纯化的细胞群体，也未在分化前确定其确切表型。本研究调查了以谱系标记缺失以及细胞表面标志物Sca1和c-Kit表达为特征的高度纯化的小鼠成体造血干细胞（HSCs），即Lin(-) Sca1(+) c-Kit(+) [LSK]细胞，是否能被诱导转变为神经元命运。当HSC(LSK)细胞在添加视黄酸的神经元分化培养基中进行体外培养时，50%的细胞表达神经祖细胞标志物巢蛋白，且没有细胞进入有丝分裂后期。对类神经元细胞的电生理记录显示，这些细胞无法产生动作电位。当HSC(LSK)细胞在体外与神经前体细胞共同培养，或被移植到野生型小鼠的纹状体或小脑中时，它们要么分化为Iba1免疫阳性的巨噬细胞/小胶质细胞，要么死亡。总之，我们证明成体HSC(LSK)细胞没有能力脱离造血谱系并分化为神经元。
