Sonic hedgehog and retinoic acid synergistically promote sensory fate specification from bone marrow-derived pluripotent stem cells
Sonic hedgehog and retinoic acid synergistically promote sensory fate specification from bone marrow-derived pluripotent stem cells
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DOI：
10.1073/pnas.0408239102
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发表时间：
2005-03-29
影响因子：
11.1
通讯作者：
Hashino, E
中科院分区：
文献类型：
--
作者：
Kondo, T;Johnson, SA;Hashino, E
最近的研究表明，从成人骨髓中分离的基质细胞在体外和体内都具有向神经细胞分化的能力。然而，骨髓基质细胞或间充质干细胞（MSC）分化成不同的神经元细胞群的能力和赋予骨髓基质细胞与神经元亚型的能力的分子因子的身份尚未阐明。在这里，我们表明，声波刺猬（Shh）和视黄酸（RA），在胚胎发育过程中周围感觉神经节附近的组织分泌的信号分子，发挥协同作用的神经主管间充质干细胞表达一套全面的神经元感觉神经元标记物。单独应用Shh或RA对这些神经元亚型标志物的表达几乎没有影响。此外，MSC与胚胎后脑/体节/耳囊条件培养基或产前耳蜗外植体的孵育促进了额外的感觉神经元标记物和突起生长的上调。这些结果确定了Shh和RA作为成年多能细胞的感觉能力因子，并建立了成年多能细胞和宿主微环境之间的相互作用在神经元亚型规范中的重要性。
Recent studies demonstrated that stromal cells isolated from adult bone marrow have the competence of differentiating into neuronal cells in vitro and in vivo. However, the capacity of marrow stromal cells or mesenchymal stem cells (MSCs)to differentiate into diverse neuronal cell populations and the identity of molecular factors that confer marrow stromal cells with the competence of a neuronal subtype have yet to be elucidated. Here, we show that Sonic hedgehog (Shh) and retinoic acid (RA), signaling molecules secreted from tissues in the vicinity of peripheral sensory ganglia during embryogenesis, exert synergistic effects on neural-competent MSCs to express a comprehensive set of glutamatergic sensory neuron markers. Application of Shh or RA alone had little or no effect on the expression of these neuronal subtype markers. In addition, incubation of MSCs with embryonic hindbrain/somite/ otocyst conditioned medium or prenatal cochlea explants promoted up-regulation of additional sensory neuron markers and process outgrowth. These results identify Shh and RA as sensory competence factors for adult pluripotent cells and establish the importance of interactions between adult pluripotent cells and the host microenvironment in neuronal subtype specification.