Shihabuddin L S, Horner P J, Ray J, Gage F H
The Salk Institute, Laboratory of Genetics, La Jolla, California 92037, USA.
J Neurosci. 2000 Dec 1;20(23):8727-35. doi: 10.1523/JNEUROSCI.20-23-08727.2000.
The adult rat spinal cord contains cells that can proliferate and differentiate into astrocytes and oligodendroglia in situ. Using clonal and subclonal analyses we demonstrate that, in contrast to progenitors isolated from the adult mouse spinal cord with a combination of growth factors, progenitors isolated from the adult rat spinal cord using basic fibroblast growth factor alone display stem cell properties as defined by their multipotentiality and self-renewal. Clonal cultures derived from single founder cells generate neurons, astrocytes, and oligodendrocytes, confirming the multipotent nature of the parent cell. Subcloning analysis showed that after serial passaging, recloning, and expansion, these cells retained multipotentiality, indicating that they are self-renewing. Transplantation of an in vitro-expanded clonal population of cells into the adult rat spinal cord resulted in their differentiation into glial cells only. However, after heterotopic transplantation into the hippocampus, transplanted cells that integrated in the granular cell layer differentiated into cells characteristic of this region, whereas engraftment into other hippocampal regions resulted in the differentiation of cells with astroglial and oligodendroglial phenotypes. The data indicate that clonally expanded, multipotent adult progenitor cells from a non-neurogenic region are not lineage-restricted to their developmental origin but can generate region-specific neurons in vivo when exposed to the appropriate environmental cues.
成年大鼠脊髓含有能够在原位增殖并分化为星形胶质细胞和少突胶质细胞的细胞。通过克隆和亚克隆分析，我们证明，与使用多种生长因子从成年小鼠脊髓分离的祖细胞不同，仅使用碱性成纤维细胞生长因子从成年大鼠脊髓分离的祖细胞表现出由其多能性和自我更新所定义的干细胞特性。源自单个起始细胞的克隆培养物可生成神经元、星形胶质细胞和少突胶质细胞，证实了亲代细胞的多能性质。亚克隆分析表明，经过连续传代、再克隆和扩增后，这些细胞仍保留多能性，表明它们具有自我更新能力。将体外扩增的细胞克隆群体移植到成年大鼠脊髓中，结果它们仅分化为神经胶质细胞。然而，异位移植到海马体后，整合到颗粒细胞层的移植细胞分化为该区域特有的细胞，而移植到其他海马区域则导致具有星形胶质细胞和少突胶质细胞表型的细胞分化。数据表明，来自非神经源性区域的经克隆扩增的多能成年祖细胞并非局限于其发育起源的谱系，而是在暴露于适当的环境线索时能够在体内生成区域特异性神经元。
