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Pools of Independently Cycling Inositol Phosphates Revealed by Pulse Labeling with <sup>18</sup>O-Water
Shape memory polymer surfaces with controllable roughness for multiscale switchable dry adhesion
Adsorption Configuration and H* Flux Modulation Enable Electrocatalytic Semihydrogenation of Alkynes with Group Tolerance in a Palladium Membrane Reactor
WNK1 mediates M-CSF-induced macropinocytosis to enforce macrophage lineage fidelity
Abstract Tissue-resident macrophages (TRM) are critical for mammalian organismal development and homeostasis. Here we report that with-no-lysine 1 (WNK1) controls myeloid progenitor fate, with Csf1r iCre-mediated Wnk1 deletion in mice (WNK1-deficient mice) resulting in loss of TRMs and causing perinatal mortality. Mechanistically, absence of WNK1 or inhibition of WNK kinase activity disrupts macrophage colony-stimulating factor (M-CSF)-stimulated macropinocytosis, thereby blocking mouse and human progenitor and monocyte differentiation into macrophages and skewing progenitor differentiation into neutrophils. Treatment with PMA rescues macropinocytosis but not macrophage differentiation of WNK-inhibited progenitors, implicating that M-CSF-stimulated, macropinocytosis-induced activation of WNK1 is required for macrophage differentiation. Finally, M-CSF-stimulated macropinocytosis triggers WNK1 nuclear translocation and concomitant increased protein expression of interferon regulatory factor (IRF)8, whereas inhibition of macropinocytosis or WNK kinase activity suppresses IRF8 expression. Our results thus suggest that WNK1 and downstream IRF8-regulated genes are important for M-CSF/macropinocytosis-mediated regulation of myeloid cell lineage commitment during TRM development and homeostasis.
A Linear Dysprosium(II) Metallocene with a High Effective Energy Barrier and Magnetic Hysteresis up to 70 Kelvin
Stable narrowband blue OLEDs by modulating frontier molecular orbital levels
Photobiocatalytic Enantioselective Benzylic C(sp <sup>3</sup> )–H Acylation Enabled by Thiamine-Dependent Enzymes via Intermolecular Hydrogen Atom Transfer
Pleiotropic and sex-specific genetic mechanisms of circulating metabolic markers
Expanded ribosomal synthesis of non-standard cyclic backbones in vitro
Reactive Oxygen Species-Instructed Supramolecular Assemblies Enable Bioorthogonally Activatable Protein Degradation for Pancreatic Cancer
ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses
Design Guidelines to Control Rippled β-Sheets versus Pleated β-Sheets in Mixed-Chirality Peptides
Elastic circular organic microcrystals prepared by photoinduced delamination
A Threose Nucleic Acid (TNA) Enzyme Catalyzing Native 3′-5′ Ligation of RNA
Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures
Abstract Genome-wide association studies (GWAS) have predominantly focused on European ancestry populations, limiting biological discoveries across diverse populations. Here we report GWAS findings from 153,950 individuals across 36 quantitative traits in the Korean Cancer Prevention Study-II (KCPS2) Biobank. We discovered 301 previously unreported genetic loci in KCPS2, including an association between thyroid-stimulating hormone and CD36 . Meta-analysis with the Korean Genome and Epidemiology Study, Biobank Japan, Taiwan Biobank, and UK Biobank identified 4588 loci that were not significant in any contributing GWAS. We describe differences in genetic architectures across these East Asian and European samples. We also highlight East Asian specific associations, including a known pleiotropic missense variant in ALDH2 , which fine-mapping identified as a likely causal variant for multiple traits. Our findings provide insights into the genetic architecture of complex traits in East Asian populations and highlight how broadening the population diversity of GWAS samples can aid discovery.