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Cell Studies on COVID-19 Autopsy Proteomics, Human Intestinal Development, Macaque Brain Map

A Chinese team takes a look at proteomic patterns in organ and tissue samples collected from 19 individuals who succumbed to COVID-19. Starting from 144 autopsy samples representing lung, spleen, liver, kidney, heart, testis, and thyroid tissues, the investigators used tandem mass tagging-based shotgun proteomic to quantify levels of almost 11,400 proteins in the autopsied organs, identifying more than 5,300 proteins with enhanced or diminished expression in samples from the SARS-CoV-2-infected individuals. They note that lung tissues from the COVID-19 patients tended to have higher-than-usual levels of an intracellular protein catabolism protein called cathepsin L1, for example, while several organs showed signs of inflammation, metabolic dysregulation, and changes to blood coagulation, angiogenesis, and other pathways. "This systematic proteomic investigation provides a rich resource for improving our understanding of the molecular pathogenesis of SARS-CoV-2 infection and offers clues for therapeutics," the authors report. 

Researchers from the University of Oxford, John Radcliffe Hospital, and Oxford University Hospital share a spatially defined transcriptome atlas spanning individual cells profiled by cell sorting and single-cell RNA sequencing in the developing human intestine. Based on nearly 76,600 individual intestinal cells from embryos at a range of developmental stages, the team's "spatiotemporal analysis resource of fetal intestinal development," or STAR-FINDer, collection revealed more than 100 cell types, highlighting functional features, cell differentiation patterns, and developmental trajectories for progenitor cells in the gut. By focusing on hundreds of genes with known ties to disease, the authors used STAR-FINDer to retrace the dynamics of intestinal disease development and cell types involved.

Finally, a team from the Chinese Academy of Sciences and Peking University presents features using a new three-dimensional map of genome architecture in the developing macaque brain. Using Hi-C mapping and other omics approaches, the researchers considered chromatin structures, chromatin interactions, and regulatory features behind corticogenesis in the macaque, comparing the three-dimensional features to those previously found in developing human and mouse brains. In particular, they point to apparent human-specific features found with the comparison — from topically associating domain (TAD) shifts to human-specific chromatin loops showing pronounced enhancer-to-enhancer interactions. "Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors," the authors report, "which may generate new transcription factor binding sites and chromatin structures in human."