Search

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cell types and their heterogeneity within the human liver, but the spatial organization at single-cell resolution has not yet been described. Here we apply multiplexed error robust fluorescent in situ hybridization (MERFISH) to map the zonal distribution of hepatocytes, spatially resolve subsets of macrophage and mesenchymal populations, and investigate the relationship between hepatocyte ploidy and gene expression within the healthy human liver. Integrating spatial information from MERFISH with the more complete transcriptome produced by single-nucleus RNA sequencing (snRNA-seq), also reveals zonally enriched receptor-ligand interactions. Finally, MERFISH and snRNA-seq analysis of fibrotic liver samples identify two hepatocyte populations that expand with injury and do not have clear zonal distributions. Together these spatial maps of the healthy and fibrotic liver provide a deeper understanding of the cellular and spatial remodeling that drives disease which, in turn, could provide new avenues for intervention and further study. Spatial transcriptomics was combined with single-nucleus RNA sequencing to annotate healthy and fibrotic human livers, improving spatial resolution of hepatocytes and receptor-ligand interactions and identifying cell populations that expand with injury. [ABSTRACT FROM AUTHOR]

Aerosol absorption of visible light has an important impact on global radiative forcing. Wildfires are one of the major sources of light-absorbing aerosol, but there remains significant uncertainty about the magnitude, wavelength dependence, and bleaching of absorption from biomass burning aerosol. We collected and analyzed data from 21 western US wildfire smoke plumes during the 2018 Western Wildfire Experiment for Cloud Chemistry, Aerosol Absorption and Nitrogen (WE-CAN) airborne measurement campaign to determine the contribution of black carbon (BC), brown carbon (BrC), and lensing to the aerosol mass absorption cross section (MAC). Comparison to commonly used parameterizations and modeling studies suggests that model overestimation of absorption is likely due to incorrect BrC refractive indices. Modelers (Wang et al., 2018; Carter et al., 2021) invoke a bleaching process that decreases the MAC of organic aerosol (OA) to offset the overestimation of absorption in models. However, no evidence of a decreasing MAC is observed in individual WE-CAN fire plumes or in aged plumes from multiple fires. A decrease in OA mass and water-soluble organic carbon (WSOC), both normalized by carbon monoxide (CO) to correct for dilution, is observed with an increasing oxygen-to-carbon (O : C) ratio and a decreasing gas-phase toluene : benzene ratio, when data from all fires are combined in half of the individual fire plumes. This results in a strong decrease in total absorption at 405 nm and a slight decrease at 660 nm with these chemical markers. These results demonstrate that changes in absorption with chemical markers of plume age are the result of decreasing OA rather than changes in the MAC of the organic material itself. While decreasing MAC or OA mass with aging could both be called bleaching and can both correct overestimation of absorption in models, it is important to distinguish between these two effects because decreasing OA mass will also decrease scattering, which will cause a significantly different net radiative effect. We also find that an average of 54 % of non-BC absorption (23 % total absorption) at 660 nm is from water-soluble BrC, confirming that BrC absorption is important across the visible spectrum. Quantification of significant BrC at red wavelengths and observation of bleaching being caused by changes in OA with O : C and toluene : benzene markers of plume age provide important improvements to our understanding of BrC and critical constraints on aerosol absorption in regional and global climate models. [ABSTRACT FROM AUTHOR]