Functional heterogeneity of ependymoglial cells in adult zebrafish telencephalon

斑马鱼端脑中的室管膜神经胶质细胞作为成体神经干细胞，也起着支持哺乳动物原浆星形胶质细胞和室管膜的作用，如代谢支持、突触包裹等。目前尚不清楚是同一个细胞具有这两种功能，还是不同的种群提供了不同的功能。我们前瞻性地分离了两个室管膜神经胶质细胞群，并比较了它们的转录本。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性原浆星形胶质细胞(胶质原生室管膜胶质细胞)的特征。在这笔赠款中，我们将使用转录组和代谢分析进一步描述这两个群体的特征。我们将进行这两个种群的遗传命运图谱，解决它们在完整的鱼脑中的潜力，并通过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群体的起源，并评估指定这两个室管膜神经胶质群体的分子途径。在这项提议中，我们将利用斑马鱼端脑的独特特征，即真正的胶质细胞和干细胞在同一个生态位中共存，来推断脊椎动物神经系的出现，并为哺乳动物的进一步分析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.