Castillo, S. P. | bioRxiv Science

bioRxiv2021

Glioblastoma cell fate is differentially regulated by the microenvironments of the tumour bulk and infiltrative margin

Glioblastoma recurrence originates from invasive cells at the tumour margin that escape surgical debulking, but their biology remains poorly understood. Here we generated three somatic mouse models recapitulating the main glioblastoma driver mutations to characterise margin cells. We find that, regardless of genetics, tumours converge on a common set of neural- like cellular states. However, bulk and margin display distinct neurogenic patterns and immune microenvironments. The margin is immune-cold and preferentially follows developmental-like trajectories to produce astrocyte-like cells. In contrast, injury-like programmes dominate in the bulk, are associated with immune infiltration and generate lowly-proliferative injured neural progenitor-like (iNPCs) cells. In vivo label-retention approaches further demonstrate that iNPCs account for a significant proportion of dormant glioblastoma cells and are induced by interferon signalling within T-cell niches. These findings indicate that tumour region is a major determinant of glioblastoma cell fate and therapeutic vulnerabilities identified in bulk may not extend to the margin residuum.

cancer biology↗

bioRxiv2020

NetworkExtinction: an R package to explore the propagation of extinctions through complex ecological networks

O_LIEarths biosphere is currently undergoing drastic reorganisation as a consequence of the sixth mass extinction brought on by the Anthropocene. Impacts of local and regional extirpation of species have been demonstrated to propagate through the complex interaction networks they are part of, subsequently leading to secondary extinctions, exacerbating biodiversity loss. Contemporary ecological theory has developed several measures to analyse the structure and robustness of ecological networks under biodiversity loss. However, a toolbox for direct simulation and quantification of extinction cascades and the creation of novel interactions (i.e. rewiring) remains absent. C_LIO_LIHere, we present NetworkExtinction - a novel R package which we have developed to explore the propagation of species extinctions sequences through ecological networks as well as quantify the effects of rewiring potential in response to primary species extinctions. With NetworkExtinction we have integrated ecological theory and computational simulations to develop functionality with which users may analyze and visualize the structure and robustness of ecological networks. The core functions introduced with NetworkExtinction focus on simulations of sequential primary extinctions and associated secondary extinctions while allowing for user-specified secondary extinction thresholds and realisation of rewiring potential. C_LIO_LIWith the package NetworkExtinction, users can estimate the robustness of ecological networks after performing species extinction routines based on several algorithms. Moreover, users can compare the number of simulated secondary extinctions against a null model of random extinctions. In-built visualizations enable graphing topological indices calculated by the deletion sequence functions after each simulation step. Finally, the user can define the degree distribution of the network by fitting different common distributions. Here, we illustrate the use of the package and its outputs by analyzing a Chilean coastal marine food web. C_LIO_LINetworkExtinction is a compact and easy-to-use R package with which users can quantify changes in ecological network structure in response to different patterns of species loss, thresholds, and rewiring potential. Therefore, this package is particularly useful to evaluate ecosystem responses to anthropogenic and environmental perturbations that produce non-random species extinctions. C_LI

ecology↗