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.

The investigation of the mechanism of insomnia could provide the basis for improved understanding and treatment of insomnia. The aim of this study is to investigate the abnormal functional connectivity throughout the entire brain of insomnia patients, and analyze the global distribution of these abnormalities. Whole brains of 50 patients with insomnia and 40 healthy controls were divided into 116 regions and abnormal connectivities were identified by comparing the Pearson’s correlation coefficients of each pair using general linear model analyses with covariates of age, sex, and duration of education. In patients with insomnia, regions that relate to wakefulness, emotion, worry/rumination, saliency/attention, and sensory-motor showed increased positive connectivity with each other; however, regions that often restrain each other, such as regions in salience network with regions in default mode network, showed decreased positive connectivity. Correlation analysis indicated that some increased positive functional connectivity was associated with the Self-Rating Depression Scale, Insomnia Severity Index, and Pittsburgh Sleep Quality Index scores. According to our findings, increased and decreased positive connectivities suggest function strengthening and function disinhibition, respectively, which offers a parsimonious explanation for the hyperarousal hypothesis in the level of the whole-brain functional connectivity in patients with insomnia.

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Accumulating evidence from neuroimaging studies suggests that primary insomnia (PI) affects interregional neural coordination of multiple interacting functional brain networks. However, a complete understanding of the whole-brain network organization from a system-level perspective in PI is still lacking. To this end, we investigated in topological organization changes in brain functional networks in PI. 36 PI patients and 38 age-, sex-, and education-matched healthy controls were recruited. All participants underwent a series of neuropsychological assessments and resting-state functional magnetic resonance imaging scans. Individual whole-brain functional network were constructed and analyzed using graph theory-based network approaches. There were no significant differences with respect to age, sex, or education between groups (P > 0.05). Graph-based analyses revealed that participants with PI had a significantly higher total number of edges (P = 0.022), global efficiency (P = 0.014), and normalized global efficiency (P = 0.002), and a significantly lower normalized local efficiency (P = 0.042) compared with controls. Locally, several prefrontal and parietal regions, the superior temporal gyrus, and the thalamus exhibited higher nodal efficiency in participants with PI (P < 0.05, false discovery rate corrected). In addition, most of these regions showed increased functional connectivity in PI patients (P < 0.05, corrected). Finally, altered network efficiency was correlated with neuropsychological variables of the Epworth Sleepiness Scale and Insomnia Severity Index in patients with PI. PI is associated with abnormal organization of large-scale functional brain networks, which may account for memory and emotional dysfunction in people with PI. These findings provide novel implications for neural substrates associated with PI.