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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Neurodevelopment
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1504047
This article is part of the Research Topic Therapeutic Potential of Adult Neurogenesis in Neurodegenerative and Neuropsychiatric Disorders View all 4 articles

High spatial resolution gene expression profiling and characterization of neuroblasts migrating in the peri-injured cortex using photoisolation chemistry

Provisionally accepted
Takuya Miyamoto Takuya Miyamoto 1Kazuya Kuboyama Kazuya Kuboyama 1Mizuki Honda Mizuki Honda 2Yasuyuki Ohkawa Yasuyuki Ohkawa 3Shinya Oki Shinya Oki 4Kazunobu Sawamoto Kazunobu Sawamoto 1*
  • 1 Nagoya City University, Nagoya, Japan
  • 2 Hiroshima University, Hiroshima, Hiroshima, Japan
  • 3 Kyushu University, Fukuoka, Fukuoka, Japan
  • 4 Kumamoto University, Kumamoto, Kumamoto, Japan

The final, formatted version of the article will be published soon.

    In the ventricular-subventricular-zone (V-SVZ) of the postnatal mammalian brain, immature neurons (neuroblasts) are generated from neural stem cells throughout their lifetime. These V-SVZ-derived neuroblasts normally migrate to the olfactory bulb through the rostral migratory stream, differentiate into interneurons, and are integrated into the preexisting olfactory circuit. When the brain is injured, some neuroblasts initiate migration toward the lesion and attempt to repair the damaged neuronal circuitry, but their low regeneration efficiency prevents functional recovery. Elucidation of the molecular basis of neuroblast migration toward lesions is expected to lead to the development of new therapeutic strategies for brain regenerative medicine. Here, we show gene expression profiles of neuroblasts migrating in the peri-injured cortex compared with those migrating in the V-SVZ using photo-isolation chemistry, a method for spatial transcriptome analysis. Differentially expressed gene analysis showed that the expression levels of 215 genes (97 upregulated and 118 downregulated genes) were significantly different in neuroblasts migrating in the peri-injured cortex from those migrating in the V-SVZ. Gene Ontology analysis revealed that in neuroblasts migrating in the periinjured cortex, expression of genes involved in regulating migration direction and preventing cell death was upregulated, while the expression of genes involved in cell proliferation and maintenance of the immature state was downregulated. Indeed, neuroblasts migrating in the peri-injured cortex had significantly lower Cyclin D2 mRNA and Ki67 protein expression levels than those in the V-SVZ. In the injured brain, amoeboid microglia/macrophages expressed transforming growth factor-β (TGF-β), and neuroblasts migrating in the peri-injured cortex expressed TGF-β receptors. Experiments using primary cultured neuroblasts showed that application of TGF-β significantly decreased proliferating cells labeled with BrdU. These data suggest that the proliferative activity of neuroblasts migrating toward lesions is suppressed by TGF-β secreted from cells surrounding the lesion. This is the first comprehensive study characterizing the gene expression profiles of neuroblasts migrating in the peri-injured cortex.

    Keywords: postnatal neurogenesis, ventricular-subventricular zone, neuroblasts, Spatial transcriptome, Neuronal regeneration

    Received: 30 Sep 2024; Accepted: 04 Dec 2024.

    Copyright: © 2024 Miyamoto, Kuboyama, Honda, Ohkawa, Oki and Sawamoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kazunobu Sawamoto, Nagoya City University, Nagoya, Japan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.