Abstract：
The African turquoise killifish (Nothobranchius furzeri) combines a short lifespan with spontaneous age-associated loss of neuro-regenerative capacity, an intriguing trait atypical for a teleost. The impact of aging on the cellular composition of the adult stem cell niches, leading to this dramatic decline in the postnatal neuro- and gliogenesis, remains elusive. Single-cell RNA sequencing of the telencephalon of young adult female killifish of the short-lived GRZ-AD strain unveiled progenitors of glial and non-glial nature, different excitatory and inhibitory neuron subtypes, as well as non-neural cell types. Sub-clustering of the progenitors identified four radial glia (RG) cell types, two non-glial progenitor (NGP) and four intermediate (intercell) cell states. Two astroglia-like, one ependymal, and one neuroepithelial-like (NE) RG subtype were found at different locations in the forebrain in line with their role, while proliferative, active NGPs were spread throughout. Lineage inference pointed to NE-RG and NGPs as start and intercessor populations for glio- and neurogenesis. Upon aging, single-cell RNA sequencing revealed major perturbations in the proportions of the astroglia and intercell states, and in the molecular signatures of specific subtypes, including altered MAPK, mTOR, Notch, and Wnt pathways. This cell catalog of the young regeneration-competent killifish telencephalon, combined with the evidence for aging-related transcriptomic changes, presents a useful resource to understand the molecular basis of age-dependent neuroplasticity. This data is also available through an online database (killifishbrain_scseq).
摘要：
非洲绿松石鱼（Nothobranchiusfurzeri）结合了短寿命和自发的与年龄相关的神经再生能力丧失，一种有趣的特征，不典型的硬骨鱼。衰老对成体干细胞壁龛细胞组成的影响，导致出生后神经和神经胶质生成的急剧下降，仍然难以捉摸。短寿命GRZ-AD菌株的成年雌性killifish的端脑的单细胞RNA测序揭示了神经胶质和非神经胶质性质的祖细胞，不同的兴奋性和抑制性神经元亚型，以及非神经细胞类型。祖细胞的亚聚类确定了四种放射状神经胶质（RG）细胞类型，两个非神经胶质祖细胞（NGP）和四个中间（细胞间）细胞状态。两个星形胶质细胞，一个室管膜,在前脑的不同位置发现了一种神经上皮样（NE）RG亚型，虽然增殖，活跃的NGP遍布各地。谱系推断指出，NE-RG和NGP是神经胶质和神经发生的起始和代言人群体。随着年龄的增长，单细胞RNA测序揭示了星形胶质细胞和细胞间状态比例的主要扰动，在特定亚型的分子特征中，包括改变的MAPK,mTOR,缺口,和Wnt途径。这个细胞目录的年轻再生能力的killifish端脑，结合衰老相关转录组变化的证据，提供了一个有用的资源来理解年龄依赖性神经可塑性的分子基础。该数据也可通过在线数据库（killifishbrain_scseq）获得。
