Constructing and deconstructing GATA2-regulated cell fate programs to establish developmental trajectories
By elevating levels of the GATA2 transcription factor in hematopoietic progenitor cells, a transcriptional enhancer establishes multilineage differentiation potential. During embryogenesis, deleting the enhancer upregulates innate immune machinery and deconstructs multilineage potential to favor monocytic differentiation.
The authors reveal a mechanism of SIgA–microbiota interaction in the adult human gut. They describe antibodies with a high capacity to bind phylogenetically distant members of the microbiota. Such cross-species reactivity does not correlate with antibody polyreactivity but crucially depends on somatic mutations.
Brief Definitive Report
This work describes the spatiotemporal orchestration of recently recruited monocyte-derived and resident macrophages during Wallerian degeneration induced by chronic constriction injury of the sciatic nerve and unveils distinct contribution of these two macrophage subsets in myelin degradation and neurofiber regeneration.
Heterozygous missense mutations in COPA underlie constitutive interferon signaling through STING, thereby defining a novel type I interferonopathy and emphasizing the importance of the ER–Golgi axis in interferon homeostasis. Based on these results, three patients have been treated with interferon signaling (JAK1) inhibitors.
Barthélemy et al. use mass spectrometry to characterize plasma tau isoforms and assess their diagnosis utility for Alzheimer’s disease. They demonstrate plasma tau phosphorylation measures of p-tau-217 and p-tau-181 are increased with amyloid. Their results support p-tau-217 is superior to p-tau-181 as an AD plasma biomarker.
A defect in COPI transport due to mutant COPA causes multimerization of STING on the Golgi and type I interferon–driven immune dysregulation in mice. Small-molecule inhibition of STING activation is a new molecular target for treating COPA syndrome.
Technical Advances and Resources
The emergence of SARS-CoV-2 has created a need for robust assays of plasma and monoclonal antibody neutralization potency. Pseudotyped HIV-1– and vesicular stomatitis virus–based reporter viruses and a replication-competent vesicular stomatitis virus/SARS-CoV-2 chimera represent useful tools to assess neutralizing antibodies.