Puglisi, M. | bioRxiv Science

bioRxiv2025

Multimodal synapse analysis reveals restricted integration of transplanted neurons remodeled by TREM2

Neuron transplantation offers a promising approach for circuit restoration after injury, but depends crucially on adequate synaptic integration. Yet, our knowledge of the effects of the host injury environment on transplanted neuron (tN) network integration remains limited. Here, we used a stab wound injury model to examine how tN synapses mature and integrate using multimodal read-outs. Morphological, ultrastructural and functional electrophysiological analysis of tN synapses indicated that tN integration and functional maturation are partially stunted. Spatial transcriptomics revealed persistent inflammatory signatures at the transplant site including Trem2 upregulation. Strikingly, in an environment devoid of TREM2, synaptic integration as well as functional maturation of tNs, including action potential maturation and spontaneous firing, were almost fully rescued. Spatial transcriptomics further showed reduced inflammatory pathways and improved maturation of tNs in Trem2-/- brains. This study highlights the importance of tackling chronic inflammation for adequate tN integration.

neuroscience↗

bioRxiv2023

Elevated Expression of srp RiPPs Across Bacterial Phyla in Marine Sponges

We investigated transcriptional activity, at a genome-resolved level, of bacterial communities in two S. officinalis and two I. felix sponges, both of which are considered high microbial abundance (HMA) sponges that harbor similar bacterial communities. Overlap of metatranscriptional data on genome-resolved metagenomic data showed that genome bins classified within the Chloroflexota and Poribacteria phyla were the most abundant and transcriptionally active. However, abundant bins in general were not the most transcriptionally active, instead less abundant bins of the same phyla were most active indicating that numerical dominance does not imply transcriptional dominance. We found that although some primary metabolic functions appeared upregulated, they were not obviously attributable to any particular bacterial species. However, assessment of transcription levels of biosynthetic gene clusters (BGCs) encoding secondary metabolites revealed a high transcription of ribosomally synthesized and post-translationally modified peptides (RiPPs) in genome bins across diverse bacterial phyla, most of which were likely srp RiPPs encoding brominated azol(in)e-containing compounds. However, the ecological role of these compounds remains elusive. IMPORTANCEMarine sponges and bacteria have formed close associations over several million years with many bacteria performing specialized functions within their sponge host. Previous studies have either assessed the genomes of a given sponge or the expression profile for a sponge holobiont as a whole. Here, we present the first genome-resolved transcriptomic study which gives us a snapshot of the transcriptional activity of individual bacteria in the context of four different sponge holobionts. Using this approach we found that the numerically dominant bacteria were not the most transcriptionally active and that relatively high expression of a ubiquitous biosynthetic gene cluster was evident in many different bacterial phyla in all four sponge samples.

ecology↗