Araujo, C. | Search bioRxiv

bioRxiv2022

M2-polarized macrophages control LSC fate by enhancing stemness, homing, immune evasion and metabolic reprogramming

While it is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones, the tumor microenvironment (TME) in acute myeloid leukemias (AML) remains poorly understood. Here, we uncover the functional and prognostic relevance of an M2-polarized macrophage compartment. Intra bone marrow co-injection of M2d-macrophages together with leukemic blasts that fail to engraft on their own now induce fatal leukemia in mice. Even a short-term two-day in vitro exposure to M2d macrophages can "train" leukemic blasts after which cells are protected against phagocytosis, display increased mitochondrial metabolism and improved in vivo homing, resulting in full-blown leukemia. Single-cell RNAseq analysis of AML associated macrophages revealed metabolic-related pathways such as Fatty Acid Oxidation and NAD+ generation as therapeutical targetable vulnerabilities. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for effective targeting strategies.

cancer biology↗

bioRxiv2020

Behavioral thermal tolerance predicts distribution pattern but not habitat use in sympatric Neotropical frogs

Environmental temperatures are a major constraint on ectotherm abundance and diversity, influencing their distribution and natural history. Comparing thermal tolerances with environmental temperatures is a simple way to estimate thermal constraints on species distributions. We investigate the potential effects of thermal tolerance on anuran local (habitat) and global distribution patterns and associated behavioral responses. We tested for differences in Voluntary Thermal Maximum of two sympatric frog species of the genus Physalaemus in the Cerrado ecoregion. For each species, we constructed models to assess the effects of period of day, duration of experiment, initial body mass, initial body temperature and heating rate on the VTMax. We mapped the difference between VTMax and maximum daily temperature (VTMax - ETMax) for each occurrence point. Physalaemus nattereri had a significantly higher VTMax than P. cuvieri. For P. nattereri, the model including only period of day was chosen as the best to explain variation in the VTMax. For P. cuvieri, no model was selected as best to predict VTMax. The VTMax - ETMax values were significantly different between species, with P. nattereri mostly found in localities that attain maximum temperatures lower than its VTMax and P. cuvieri showing the reverse pattern. Regarding habitat use, we found P. cuvieri to be slightly more abundant in open habitats than in non-open habitats, whereas P. nattereri shows the reverse pattern. The difference in VTMax values between these two species might be related to their different body sizes, but additionally might reflect their natural history, especially the way they use their habitats, and phylogenetic constraints (the species studied are in different clades within Physalaemus). Our study indicates that differences in behavioral thermal tolerance may be important in shaping local and regional distribution patterns. Furthermore, small-scale habitat use might reveal a link between behavioral thermal tolerance and natural history strategies.

ecology↗