Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration

The molecular mechanism underlying brain regeneration in vertebrates remains elusive. A team led by researchers at BGI 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. The researchers 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. The researchers further uncovered spatially defined neurons at the lesion site that may regress to an immature neuron–like state. This 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.

Development and regeneration of axolotl telencephalon

The spatially resolved single-cell transcriptome of the adult axolotl telencephalon as determined by Stereo-seq analyses (left). Upon brain injury in the highlighted lateral pallium region of the left hemisphere, a neural progenitor subpopulation at the wound site was rapidly induced and subsequently replenished lost neurons (bottom right) through a process that partially resembles neurogenesis during development (top right).

Wei X, Fu S, Li H, Liu Y, Wang S, Feng W, Yang Y, Liu X, Zeng YY, Cheng M, Lai Y, Qiu X, Wu L, Zhang N, Jiang Y, Xu J, Su X, Peng C, Han L, Lou WP, Liu C, Yuan Y, Ma K, Yang T, Pan X, Gao S, Chen A, Esteban MA, Yang H, Wang J, Fan G, Liu L, Chen L, Xu X, Fei JF, Gu Y. (2022) Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration. Science 377(6610):eabp9444. [abstract]

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