Wu Hao

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Wu
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Hao
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  • Article
    NLRP3 inflammasome assembly in neutrophils is supported by PAD4 and promotes NETosis under sterile conditions
    (Frontiers Media, 2021-03-28) Münzer, Patrick ; Negro, Roberto ; Fukui, Shoichi ; di Meglio, Lucas ; Aymonnier, Karen ; Chu, Long ; Cherpokova, Deya ; Gutch, Sarah ; Sorvillo, Nicoletta ; Shi, Lai ; Magupalli, Venkat Giri ; Weber, Alexander N. R. ; Scharf, Rüdiger E. ; Waterman, Clare M. ; Wu, Hao ; Wagner, Denisa D.
    Neutrophil extracellular trap formation (NETosis) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome assembly are associated with a similar spectrum of human disorders. While NETosis is known to be regulated by peptidylarginine deiminase 4 (PAD4), the role of the NLRP3 inflammasome in NETosis was not addressed. Here, we establish that under sterile conditions the cannonical NLRP3 inflammasome participates in NETosis. We show apoptosis-associated speck-like protein containing a CARD (ASC) speck assembly and caspase-1 cleavage in stimulated mouse neutrophils without LPS priming. PAD4 was needed for optimal NLRP3 inflammasome assembly by regulating NLRP3 and ASC protein levels post-transcriptionally. Genetic ablation of NLRP3 signaling resulted in impaired NET formation, because NLRP3 supported both nuclear envelope and plasma membrane rupture. Pharmacological inhibition of NLRP3 in either mouse or human neutrophils also diminished NETosis. Finally, NLRP3 deficiency resulted in a lower density of NETs in thrombi produced by a stenosis-induced mouse model of deep vein thrombosis. Altogether, our results indicate a PAD4-dependent formation of the NLRP3 inflammasome in neutrophils and implicate NLRP3 in NETosis under noninfectious conditions in vitro and in vivo.
  • Article
    A Wox3-patterning module organizes planar growth in grass leaves and ligules
    (Nature Research, 2023-05-04) Satterlee, James W. ; Evans, Lukas J. ; Conlon, Brianne R. ; Conklin, Phillip ; Martinez-Gomez, Jesus ; Yen, Jeffery R. ; Wu, Hao ; Sylvester, Anne W. ; Specht, Chelsea D. ; Cheng, Jie ; Johnston, Robyn ; Coen, Enrico ; Scanlon, Michael J.
    Grass leaves develop from a ring of primordial initial cells within the periphery of the shoot apical meristem, a pool of organogenic stem cells that generates all of the organs of the plant shoot. At maturity, the grass leaf is a flattened, strap-like organ comprising a proximal supportive sheath surrounding the stem and a distal photosynthetic blade. The sheath and blade are partitioned by a hinge-like auricle and the ligule, a fringe of epidermally derived tissue that grows from the adaxial (top) leaf surface. Together, the ligule and auricle comprise morphological novelties that are specific to grass leaves. Understanding how the planar outgrowth of grass leaves and their adjoining ligules is genetically controlled can yield insight into their evolutionary origins. Here we use single-cell RNA-sequencing analyses to identify a ‘rim’ cell type present at the margins of maize leaf primordia. Cells in the leaf rim have a distinctive identity and share transcriptional signatures with proliferating ligule cells, suggesting that a shared developmental genetic programme patterns both leaves and ligules. Moreover, we show that rim function is regulated by genetically redundant Wuschel-like homeobox3 (WOX3) transcription factors. Higher-order mutations in maize Wox3 genes greatly reduce leaf width and disrupt ligule outgrowth and patterning. Together, these findings illustrate the generalizable use of a rim domain during planar growth of maize leaves and ligules, and suggest a parsimonious model for the homology of the grass ligule as a distal extension of the leaf sheath margin.