RESUMEN
Spatially resolved gene expression profiling provides insight into tissue organization and cell-cell crosstalk; however, sequencing-based spatial transcriptomics (ST) lacks single-cell resolution. Current ST analysis methods require single-cell RNA sequencing data as a reference for rigorous interpretation of cell states, mostly do not use associated histology images and are not capable of inferring shared neighborhoods across multiple tissues. Here we present Starfysh, a computational toolbox using a deep generative model that incorporates archetypal analysis and any known cell type markers to characterize known or new tissue-specific cell states without a single-cell reference. Starfysh improves the characterization of spatial dynamics in complex tissues using histology images and enables the comparison of niches as spatial hubs across tissues. Integrative analysis of primary estrogen receptor (ER)-positive breast cancer, triple-negative breast cancer (TNBC) and metaplastic breast cancer (MBC) tissues led to the identification of spatial hubs with patient- and disease-specific cell type compositions and revealed metabolic reprogramming shaping immunosuppressive hubs in aggressive MBC.
RESUMEN
The secondary metabolite emodin, produced by the widely distributed invasive shrub known as the common buckthorn (Rhamnus cathartica), has been shown to produce deformities and mortality in invertebrates, fish, and amphibian larvae. Here, we describe the effects on the liver of green frog (Lithobates clamitans) tadpoles after 21 d of exposure to high concentrations of emodin in a controlled environment. Histopathologic analysis showed fibrosis, bile duct proliferation, hepatocellular swelling, and accumulations of flocculent material consistent with emodin within the gall bladder and bile ducts of exposed individuals. The extensive fibrosis produced probably impeded the blood flow within the portal triads, limiting the detoxification function of the liver and resulting in hepatocellular necrosis and premature death for the individuals exposed. Exposure to emodin in the environment could represent a significant threat to developing amphibian larvae and contribute to local declines of populations.
