首页> 外国专利> Lineage-restricted precursor cells isolated from mouse neural tube and mouse embryonic stem cells

Lineage-restricted precursor cells isolated from mouse neural tube and mouse embryonic stem cells

机译:从小鼠神经管和小鼠胚胎干细胞中分离出的沿袭限制前体细胞

摘要

A self-renewing restricted stem cell population has been identified in developing (embryonic day 13.5) spinal cords that can differentiate into multiple neuronal phenotypes, but cannot differentiate into glial phenotypes. This neuronal-restricted precursor (NRP) expresses highly polysialated or embryonic neural cell adhesion molecule (E-NCAM) and is morphologically distinct from neuroepithelial stem cells (NEP cells) and spinal glial progenitors derived from embryonic day 10.5 spinal cord. NRP cells self renew over multiple passages in the presence of fibroblast growth factor (FGF) and neurotrophin 3 (NT-3) and express a characteristic subset of neuronal epitopes. When cultured in the presence of RA and the absence of FGF, NRP cells differentiate into GABAergic, glutaminergic, and cholinergic immunoreactive neurons. NRP cells can also be generated from multipotent NEP cells cultured from embryonic day 10.5 neural tubes. Clonal analysis shows that E-NCAM immunoreactive NRP cells arise from an NEP progenitor cell that generates other restricted CNS precursors. The NEP-derived E-NCAM immunoreactive cells undergo self renewal in defined medium and differentiate into multiple neuronal phenotypes in mass and clonal culture. Thus, a direct lineal relationship exists between multipotential NEP cells and more restricted neuronal precursor cells present in vivo at embryonic day 13.5 in the spinal cord. Methods for treating neurological diseases are also disclosed.
机译:在发育中的(胚胎第13.5天)脊髓中已鉴定出一种自我更新的受限干细胞群体,可以分化为多种神经元表型,但不能分化为神经胶质表型。这种神经元限制性前体(NRP)表达高度多唾液酸化或胚胎神经细胞粘附分子(E-NCAM),在形态上不同于神经上皮干细胞(NEP细胞)和源自胚胎第10.5天脊髓的神经胶质祖细胞。在存在成纤维细胞生长因子(FGF)和神经营养蛋白3(NT-3)的情况下,NRP细胞会通过多次传代自我更新,并表达神经元表位的特征性子集。在存在RA和不存在FGF的情况下培养NRP细胞时,它们会分化为GABA能,谷氨酰胺能和胆碱能免疫反应性神经元。 NRP细胞也可以从胚胎第10.5天神经管培养的多能NEP细胞中产生。克隆分析表明,E-NCAM免疫反应性NRP细胞源自产生其他限制性CNS前体的NEP祖细胞。 NEP衍生的E-NCAM免疫反应性细胞在定义的培养基中进行自我更新,并在大规模和克隆培养中分化为多种神经元表型。因此,在胚胎的第13.5天,脊髓中多能性NEP细胞与体内存在的限制性更强的神经元前体细胞之间存在直接的线性关系。还公开了治疗神经系统疾病的方法。

著录项

相似文献

  • 专利
  • 外文文献
  • 中文文献
获取专利

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号