Cellular and Transcriptomic Analyses Identify the Source and Lineage of Regenerated Neurons in the Adult Zebrafish Telencephalon following Blunt-Force Traumatic Brain Injury

ABSTRACT: Traumatic brain injuries (TBIs) represent a large global disease burden and can result in several short- and long-term deficits. Treatment for TBIs are limited, however stem cell therapies involving either transplantation of exogenous stem cells or stimulation of endogenous stem cells have been proposed. These approaches possess issues with survival and differentiation of stem/progenitor cells, which highlights the need to elucidate mechanisms necessary for complete regeneration. Zebrafish exhibit a robust neuronal regenerative capacity following damage in various parts of the central nervous system. In this study, we use a modified blunt-force TBI (bfTBI) model, the most common type of TBI seen in the human population, to damage the adult zebrafish telencephalon and examine cellular and molecular consequences. This model induces a variety of TBI-related phenotypes across different injury severities, which mimic the pathologies observed following bfTBI in humans. Additionally, we show that after bfTBI, cells in the zebrafish telencephalon, including radial glia (RGC), non-glial neural progenitors (NPs), and neuroblasts, proliferate and differentiate into various neural cell types. We performed a snRNA-Seq analysis of the damaged and regenerating telencephalon, which revealed heterogeneity among the progenitor cells. Further, the snRNA-Seq demonstrated that quiescent radial glia became activated upon injury and yielded neural progenitor cells. To functionally assess how the regenerative process is regulated, we knocked down the expression of PdgfrB and demonstrated that it played a role in maintaining RGC quiescence. Collectively, this study provides a foundation for future studies of neuronal regeneration in the adult zebrafish telencephalon following a bfTBI.

ORGANISM(S): Danio rerio

PROVIDER: GSE278446 | GEO | 2024/10/04

REPOSITORIES: GEO