Grimaldo, E. | bioRxiv Science

bioRxiv2022

Spatial transcriptomic analysis of childhood ependymoma implicates unresolved wound healing as a driver of tumor progression

Childhood ependymoma (EPN) is a brain tumor that has seen limited improvements in outcome over past decades. The underlying cellular components of EPN have recently been revealed by single cell RNA-sequencing (scRNAseq), providing biological insights. Here we use spatial transcriptomics to comprehensively chart gene expression across the cellular landscape of posterior fossa subgroup A (PFA) EPN, the commonest and most deadly EPN variant, providing novel resolution of cellular heterogeneity and cellular interaction. We reveal that PFA are comprised of epithelial and mesenchymal histological zones each containing a diversity of cellular states. These include co-existing and spatially distinct undifferentiated progenitor-like clusters - a quiescent mesenchymal zone population, and a second highly mitotic progenitor population that is restricted to hypercellular epithelial zones. We show that myeloid cell interaction is the leading cause of mesenchymal transition in PFA, occurring in zones spatially distinct from hypoxia-induced mesenchymal transition, and these distinct EMT-initiating processes were replicated in in-vitro models of PFA. Collectively, our transcriptomic and functional analyses mirror the processes of normal wound healing where PFA mesenchymal and epithelial zones interact with immune subpopulations in cycle of persistent tissue damage response and mitogenic re-epithelialization signals. Spatial transcriptomics advances our understanding of PFA biology, implicating a "wound that will not heal" process as a driver of tumor progression, a new concept that could provide novel targets for effective therapeutic intervention. SignificanceSpatial transcriptomic analysis of the ependymoma tumor microenvironment identifies novel cell populations and interactions, implicating unresolved wound healing as a clinically actionable driver of tumor progression in this refractory childhood brain tumor.

cancer biology↗

bioRxiv2020

Effect of mechanical properties of monofilament twines on the catch efficiency of biodegradable gillnets.

Gillnets made of the biodegradable resin polybutylene succinate co-adipate-co-terephthalate (PBSAT) were tested under commercial fishing conditions to compare their fishing performance with that of conventional nylon polyamide (PA) gillnets. Both types of gillnets were made of 0.55 mm Ø monofilaments. However, since the biodegradable nets are weaker than nylon PA nets when using the same monofilament diameter, we also used biodegradable nets made of 0.60 mm Ø monofilament that had a similar tensile strength to the 0.55 mm Ø nylon PA nets. The relative catch efficiency of the different gillnet types was evaluated over the 2018 autumn fishing season for saithe and cod in northern Norway. For cod, both biodegradable gillnets (0.55 and 0.60 mm) had a significantly lower catch efficiency compared to the traditional nylon PA net (0.55 mm) with estimated catch efficiencies of 62.38% (CI: 50.55–74.04) and 54.96% (CI: 35.42–73.52) compared with the nylon PA net, respectively. Similarly for saithe, both biodegradable gillnets (0.55 and 0.60 mm) had a lower estimated catch efficiency compared to the traditional nylon PA net (0.55 mm) with estimated catch efficiencies of 83.40% (71.34–94.86) and 83.87% (66.36–104.92), compared with the nylon PA net, respectively. Tensile strength does not explain the differences in catch efficiency between the two gillnet types, since increasing the twine diameter of the biodegradable gillnets (to match the strength of nylon PA gillnets) did not yield similar catch efficiencies. However, the elasticity and stiffness of the materials may be responsible for the differences in catch efficiency between the nylon PA and biodegradable gillnets.View Full Text

scientific communication and education↗