A collection of the primary structures of roughly 30,000 unique proteoforms expressed from 1,690 human genes across 21 cell types and plasma from human blood and bone marrow is presented in Science this week. Created by a Northwestern University-led team, the Blood Proteoform Atlas represents a resource that can be used to understand the spatial and temporal dynamics of proteins that operate in human tissue. The atlas, its developers write, indicates that proteoforms better describe protein-level biology and are more specific indicators of differentiation than their corresponding proteins, which are more broadly expressed across cell types. To show the atlas' clinical potential, the researchers use it to identify cell and proteoform signatures that distinguish normal liver transplant function from acute rejection and other causes of graft dysfunction. "This cellular and molecular specificity can help advance the future of protein-level diagnostics and broader goals for understanding human biology," they conclude.
A single-cell atlas of normal and malformed human brain vasculature is published in Science by a University of California, San Francisco-led team this week. To build the atlas, the investigators profiled transcriptomes of 181,388 cells from the adult human cerebrovasculature including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. Among their discoveries were conservation of endothelial molecular zonations essential to arteriovenous phenotypic change and expanded cellular diversity of brain perivascular cells, including fibromyocytes not previously identified in the cerebrovasculature. To demonstrate the atlas' clinical utility, the scientists use it to define cellular and gene expression changes in brain arteriovenous malformations — a leading cause of stroke in young people — and identify pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. "Our results should inform future studies in other brain regions or cerebrovascular diseases to accelerate mechanistic understanding and therapeutic targeting of the human cerebrovasculature," they write.