Single cell sequencing of radial glia progeny reveals the diversity of newborn neurons in the adult zebrafish brain
Single cell sequencing of radial glia progeny reveals the diversity of newborn neurons in the adult zebrafish brain
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DOI：
10.1242/dev.185595
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发表时间：
2020-01-01
期刊：
影响因子：
4.6
通讯作者：
Brand, Michael
中科院分区：
文献类型：
--
作者：
Lange, Christian;Rost, Fabian;Brand, Michael
斑马鱼表现出广泛而明显的成年神经发生，这是其中枢神经系统损伤后再生能力的基础。然而，成年新生神经元的细胞身份和生物学特性在大多数脑区是难以捉摸的。在这里，我们使用放射状胶质细胞后代的短期谱系追踪，前瞻性地从体内平衡的成人前脑的her4.1（+）放射状胶质细胞谱系中分离新生神经元。利用单细胞测序对放射状胶质细胞、新生神经元和成熟神经元进行转录组分析，发现了不同的转录谱，包括每个群体的新标记。具体来说，我们检测到两种独立的新生神经元类型，它们表现出细胞命运承诺和位置的多样性。进一步的分析表明，这些细胞类型与哺乳动物大脑中的神经源性细胞同源，确定了增殖的放射状胶质细胞的神经源性承诺，并表明成年斑马鱼端脑产生谷氨酸能投射神经元。因此，我们前瞻性地从成年斑马鱼前脑中分离出成年新生神经元，鉴定了成年大脑中新生神经元和成熟神经元的标记物，揭示了成年新生神经元之间的内在异质性及其与哺乳动物成年神经源性细胞类型的同源性。
Zebrafish display widespread and pronounced adult neurogenesis, which is fundamental for their regeneration capability after central nervous system injury. However, the cellular identity and the biological properties of adult newborn neurons are elusive for most brain areas. Here, we have used short-term lineage tracing of radial glia progeny to prospectively isolate newborn neurons from the her4.1(+) radial glia lineage in the homeostatic adult forebrain. Transcriptome analysis of radial glia, newborn neurons and mature neurons using single cell sequencing identified distinct transcriptional profiles, including novel markers for each population. Specifically, we detected two separate newborn neuron types, which showed diversity of cell fate commitment and location. Further analyses showed that these cell types are homologous to neurogenic cells in the mammalian brain, identified neurogenic commitment in proliferating radial glia and indicated that glutamatergic projection neurons are generated in the adult zebrafish telencephalon. Thus, we prospectively isolated adult newborn neurons from the adult zebrafish forebrain, identified markers for newborn and mature neurons in the adult brain, and revealed intrinsic heterogeneity among adult newborn neurons and their homology with mammalian adult neurogenic cell types.