Spatiotemporal transcriptomic map of ischemic brain injury. Daniel Zucha, Pavel Abaffy, Denisa Kirdajova, Daniel Jirak, Miroslava Anderova, Mikael Kubista, Lukas Valihrach. bioRxiv 2023.03.28.534553; doi: https://doi.org/10.1101/2023.03.28.534553.
Characterization of regeneration initiating cells during Xenopus laevis tail regeneration. Radek Sindelka, Pavel Abaffy, Daniel Zucha, Ravindra Naraine, Daniel Kraus, Jiri Netusil, Karel Smetana Jr., Lacina Lukas, Berwini Beduya Endaya, Jiri Neuzil, Martin Psenicka, Mikael Kubista. bioRxiv 2023.03.30.534908; doi: https://doi.org/10.1101/2023.03.30.534908.
The role of non-neuronal cells in the resolution of cerebral ischemia remains to be fully understood. To decode key cellular processes that occur after ischemia, we performed spatial and single-cell transcriptomic profiling of mouse brain tissue during the first week of injury. Cortical gene expression was severely disrupted, being defined by inflammation and cell death in the lesion core, and glial scar formation on the periphery. For each of the three major glial populations, an inflammatory-responsive state, resembling the reactive states observed in neurodegenerative contexts, was documented. The recovered spectrum of ischemia-induced oligodendrocyte states supports the emerging hypothesis that oligodendrocytes actively respond to and modulate the neuroinflammatory stimulus. Thus, we present a landmark transcriptomic dataset that provides a comprehensive view of spatiotemporal organization of processes in the post-ischemic brain and documents the conservation of glial response in CNS pathology.
Embryos are regeneration and wound healing masters. They not only rapidly close their wounds, remodel injured tissue without a scar, but also regenerate body parts. Many animal models with variable regenerative capabilities have already been studied. Additionally, with the introduction of high throughput techniques, novel regeneration mechanisms including genes and signaling pathways, and specialized cell types required for regeneration control in spatial and temporal aspects have been identified. Until now our knowledge has been limited to primarily the late phases of regeneration (> 1 day post injury). In this paper, we reveal the critical steps for regeneration initiation. We have discovered Regeneration Initiating Cells (RICs) using single cell and spatial transcriptomic analyses during tail regeneration in Xenopus laevis. RICs are formed transiently from the basal epidermal cells and are critical for the modification of the surrounding extracellular matrix to allow for migration of other cell types such as regeneration organizing cells that further promote regeneration. Absence or deregulation of RICs leads to excessive extracellular matrix deposition and regeneration defects.