Robins Sarah C, Trudel Eric, Rotondi Olivia, Liu Xiaohong, Djogo Tina, Kryzskaya Darya, Bourque Charles W, Kokoeva Maia V
Department of Medicine, McGill University, Montreal, Canada.
PLoS One. 2013 Oct 29;8(10):e78236. doi: 10.1371/journal.pone.0078236. eCollection 2013.
Accumulating evidence suggests that the adult murine hypothalamus, a control site of several fundamental homeostatic processes, has neurogenic capacity. Correspondingly, the adult hypothalamus exhibits considerable cell proliferation that is ongoing even in the absence of external stimuli, and some of the newborn cells have been shown to mature into cells that express neuronal fate markers. However, the identity and characteristics of proliferating cells within the hypothalamic parenchyma have yet to be thoroughly investigated. Here we show that a subset of NG2-glia distributed throughout the mediobasal hypothalamus are proliferative and express the stem cell marker Sox2. We tracked the constitutive differentiation of hypothalamic NG2-glia by employing genetic fate mapping based on inducible Cre recombinase expression under the control of the NG2 promoter, demonstrating that adult hypothalamic NG2-glia give rise to substantial numbers of APC+ oligodendrocytes and a smaller population of HuC/D+ or NeuN+ neurons. Labelling with the cell proliferation marker BrdU confirmed that some NG2-derived neurons have proliferated shortly before differentiation. Furthermore, patch-clamp electrophysiology revealed that some NG2-derived cells display an immature neuronal phenotype and appear to receive synaptic input indicative of their electrical integration in local hypothalamic circuits. Together, our studies show that hypothalamic NG2-glia are able to take on neuronal fates and mature into functional neurons, indicating that NG2-glia contribute to the neurogenic capacity of the adult hypothalamus.
越来越多的证据表明，成年小鼠下丘脑作为几个基本稳态过程的控制部位，具有神经发生能力。相应地，成年下丘脑表现出相当程度的细胞增殖，即使在没有外部刺激的情况下这种增殖也在持续进行，并且一些新生细胞已被证明可成熟为表达神经元命运标记的细胞。然而，下丘脑实质内增殖细胞的身份和特征尚未得到彻底研究。在这里，我们表明分布于整个中基底下丘脑的一部分NG2胶质细胞具有增殖能力并表达干细胞标记物Sox2。我们通过基于在NG2启动子控制下的诱导型Cre重组酶表达进行遗传命运图谱分析，追踪了下丘脑NG2胶质细胞的组成性分化，证明成年下丘脑NG2胶质细胞可产生大量APC+少突胶质细胞以及少量HuC/D+或NeuN+神经元。用细胞增殖标记物BrdU标记证实，一些源自NG2的神经元在分化前不久已经增殖。此外，膜片钳电生理学研究表明，一些源自NG2的细胞表现出不成熟的神经元表型，并且似乎接受了表明它们在局部下丘脑回路中电整合的突触输入。总之，我们的研究表明，下丘脑NG2胶质细胞能够获得神经元命运并成熟为功能性神经元，这表明NG2胶质细胞对成年下丘脑的神经发生能力有贡献。
