Functional heterogeneity of ependymoglial cells in adult zebrafish telencephalon

斑马鱼端脑内的室管膜胶质细胞不仅具有成体神经干细胞的功能，还具有哺乳动物原生质星形胶质细胞和室管膜的支持作用，如代谢支持、突触包裹等。目前尚不清楚是同一细胞具有这两种功能，还是不同的细胞群提供不同的功能。我们前瞻性地分离了两个室管膜胶质种群并比较了它们的转录组。转录组分析表明，一个群体可以提供新的神经元（神经源性室管膜胶质细胞），而另一个群体具有骨原质星形胶质细胞（胶质源性室管膜胶质细胞）的特征。在这项资助中，我们将使用转录组和代谢分析进一步表征这两个群体。我们将对这两个种群进行遗传命运定位，以确定它们在完整鱼脑中的潜力，并利用消融实验评估它们的功能重要性。最后，我们将在发育过程中讨论这两个种群的起源，并评估指定这两个室管膜胶质种群的分子途径。在本研究中，我们将利用斑马鱼端脑的独特特征，即真正的神经胶质细胞和干细胞在同一生态位中共存，推断脊椎动物神经谱系的出现，并为进一步分析哺乳动物神经谱系提供分子和细胞基础。

The ependymoglial cells in the zebrafish telencephalon act as adult neural stem cells, but also serve the supporting role of mammalian protoplasmic astrocytes and ependyma such as metabolic support, synapse enwrapping, etc. At present it is not clear if the same cell has both functions or if different populations provide different functions. We have prospectively isolated two ependymoglial populations and compared their transcriptomes. The transcriptome analysis suggests that one population could provide new neurons (neurogenic ependymoglia), while the other has the characteristics of the bone fide protoplasmic astrocytes (gliogenic ependymoglia). Within this grant, we will further characterize these two populations using the transcriptome and metabolic analysis. We will perform the genetic fate mapping of these two populations addressing their potential in the intact fish brain and assess their functional importance using the ablation experiments. Finally, we will address the origin of the two populations during the development and assess the molecular pathways specifying these two ependymoglial populations. Within this proposal, we will utilize the unique feature of the zebrafish telencephalon, the coexistence of the bona fide glial cells and stem cells in the same niche, to infer the emergence of neural lineages in vertebrates and provide the molecular and cellular basis for the further analysis in mammals.