BGI-Hangzhou, Hangzhou 310012, China.
BGI-Shenzhen, Shenzhen 518103, China.
Science. 2022 Sep 2;377(6610):eabp9444. doi: 10.1126/science.abp9444.
The molecular mechanism underlying brain regeneration in vertebrates remains elusive. We performed spatial enhanced resolution omics sequencing (Stereo-seq) to capture spatially resolved single-cell transcriptomes of axolotl telencephalon sections during development and regeneration. Annotated cell types exhibited distinct spatial distribution, molecular features, and functions. We identified an injury-induced ependymoglial cell cluster at the wound site as a progenitor cell population for the potential replenishment of lost neurons, through a cell state transition process resembling neurogenesis during development. Transcriptome comparisons indicated that these induced cells may originate from local resident ependymoglial cells. We further uncovered spatially defined neurons at the lesion site that may regress to an immature neuron-like state. Our work establishes spatial transcriptome profiles of an anamniote tetrapod brain and decodes potential neurogenesis from ependymoglial cells for development and regeneration, thus providing mechanistic insights into vertebrate brain regeneration.
脊椎动物大脑再生的分子机制仍难以捉摸。我们进行了空间增强分辨率组学测序（Stereo-seq），以捕获蝾螈端脑发育和再生过程中节段的空间分辨单细胞转录组。注释的细胞类型表现出不同的空间分布、分子特征和功能。我们在创伤部位发现了一个由诱导的室管膜细胞簇，作为潜在神经元补充的祖细胞群体，通过类似于发育过程中的神经发生的细胞状态转变过程。转录组比较表明，这些诱导细胞可能来自局部常驻室管膜细胞。我们进一步揭示了损伤部位的空间限定神经元，它们可能退回到不成熟的神经元样状态。我们的工作建立了无羊膜四足动物大脑的空间转录组图谱，并解码了室管膜细胞的潜在神经发生，以促进发育和再生，从而为脊椎动物大脑再生提供了机制见解。
