Department of Neuroscience, Director, Jefferson Stem Cell and Regenerative Neuroscience Center, Vickie and Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
J Neurosci. 2021 Jun 23;41(25):5331-5337. doi: 10.1523/JNEUROSCI.0340-21.2021. Epub 2021 May 6.
In 1981, I published a paper in the first issue of with my postdoctoral mentor, Richard Bunge. At that time, the long-standing belief that each neuron expressed only one neurotransmitter, known as Dale's Principle (Dale, 1935), was being hotly debated following a report by French embryologist Nicole Le Douarin showing that neural crest cells destined for one transmitter phenotype could express characteristics of another if transplanted to alternate sites in the developing embryo (Le Douarin, 1980). In the Bunge laboratory, we were able to more directly test the question of phenotypic plasticity in the controlled environment of the tissue culture dish. Thus, in our paper, we grew autonomic catecholaminergic neurons in culture under conditions which promoted the acquisition of cholinergic traits and showed that cells did not abandon their inherited phenotype to adopt a new one but instead were capable of dual transmitter expression. In this Progressions article, I detail the path that led to these findings and how this study impacted the direction I followed for the next 40 years. This is my journey from phenotypic plasticity to the promise of a stem cell therapy.
1981 年，我与我的博士后导师理查德·邦格（Richard Bunge）在《进展》的第一期上发表了一篇论文。当时，法国胚胎学家妮可·勒杜阿林（Nicole Le Douarin）的一份报告引发了一场激烈的争论，该报告表明，神经嵴细胞如果被移植到胚胎发育的不同部位，就有可能表现出另一种递质表型的特征，而这种长期存在的观点认为，每个神经元只表达一种神经递质，这被称为戴尔原则（Dale，1935）。在邦格实验室，我们能够在组织培养皿的受控环境中更直接地测试表型可塑性的问题。因此，在我们的论文中，我们在促进胆碱能特征获得的条件下培养自主儿茶酚胺能神经元，并表明细胞不会放弃其遗传表型去采用新的表型，而是能够进行双重递质表达。在这篇进展文章中，我详细描述了导致这些发现的途径，以及这项研究如何影响我在接下来 40 年中所遵循的方向。这是我从表型可塑性到干细胞治疗的承诺的旅程。
