Reversal of developmental restrictions in neural crest lineages:: Transition from Schwann cells to glial-melanocytic precursors in vitro
Reversal of developmental restrictions in neural crest lineages:: Transition from Schwann cells to glial-melanocytic precursors in vitro
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DOI：
10.1073/pnas.0831229100
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发表时间：
2003-04-29
影响因子：
11.1
通讯作者：
Le Douarin, NM
中科院分区：
文献类型：
--
作者：
Dupin, E;Real, C;Le Douarin, NM
无脊椎动物胚胎中，神经嵴（NC）产生的谱系多样化在很大程度上受到环境因素的控制。在之前的工作中，我们表明内皮素 3 (ET3) 肽有利于体外神经胶质细胞和黑素细胞 NC 前体的发育。该因子还能够诱导培养的表皮色素细胞的增殖及其向神经胶质细胞的转化。因此，ET3 强烈促进前体黑素细胞和神经胶质细胞表型的出现，并作用于这些表型的维持。在目前的工作中，我们探索了 ET3 将神经胶质细胞重编程为黑素细胞的能力。从鹌鹑胚胎的坐骨神经中分离出表达神经胶质特异性标记物[例如施万细胞髓磷脂蛋白(SMP)]的施万细胞并进行体外培养。我们发现，在纯化的 SMP 表达细胞培养物中，ET3 促进细胞生长和黑素细胞分化标记物的连续表达，而它对来自同一神经的 SMP 阴性细胞没有显着影响。此外，我们还提供了克隆培养物中分化的雪旺细胞向黑素细胞转变的证据。这种转变涉及黑色素母细胞/黑色素细胞、神经胶质细胞和带有两种表型分化标记的细胞的混合后代的产生。因此，暴露于 ET3 的雪旺细胞通过回复到双能神经胶质-黑素细胞 NC 前体阶段而转分化为黑素细胞。这些发现表明，NC 衍生的色素和神经胶质细胞在体外表型不稳定，可能会经历前体层次结构的逆转，以发挥双能干细胞的作用。
Invertebrate embryos, diversification of the lineages arising from the neural crest (NC) is controlled to a large extent by environmental factors. In previous work, we showed that endothelin 3 (ET3) peptide favors the development of glial and melanocytic NC precursors in vitro. This factor is also capable of inducing proliferation of cultured epidermal pigment cells and their conversion to glia. ET3 therefore strongly promotes the emergence of melanocytic and glial phenotypes from precursors and acts on the maintenance of these phenotypes. In the present work, we explored the capacity of ET3 to reprogram glial cells into melanocytes. Schwann cells expressing glial-specific markers [such as the Schwann cell myelin protein (SMP)] were isolated from sciatic nerves of quail embryos and cultured in vitro. We found that ET3 promotes cell growth and sequential expression of melanocyte differentiation markers in cultures of purified SMP-expressing cells, whereas it had no significant effect on SMP-negative cells from the same nerves. Moreover, we provide evidence for the transition of differentiated Schwann cells to melanocytes in clonal cultures. This transition involves the production of a mixed progeny of melanoblasts/melanocytes, glia, and cells bearing differentiation markers of both phenotypes. Therefore, Schwann cells exposed to ET3 transdifferentiate to melanocytes through reversion to the stage of bipotent glial-melanocytic NC precursors. These findings show that NC-derived pigment and glial cells are phenotypically unstable in vitro and may undergo reversal of precursor hierarchy to function as bipotent stem cells.