Florian Wimmers, Allison R Burrell, Yupeng Feng, Hong Zheng, Prabhu S Arunachalam, Mengyun Hu, Sara Spranger, Lindsay E Nyhoff, Devyani Joshi, Meera Trisal, Mayanka Awasthi, Lorenza Bellusci, Usama Ashraf, Sangeeta Kowli, Katherine C Konvinse, Emily Yang, Michael Blanco, Kathryn Pellegrini, Gregory Tharp, Thomas Hagan, R Sharon Chinthrajah, Tran T Nguyen, Alba Grifoni, Alessandro Sette, Kari C Nadeau, David B Haslam, Steven E Bosinger, Jens Wrammert, Holden T Maecker, Paul J Utz, Taia T Wang, Surender Khurana, Purvesh Khatri, Mary A Staat, Bali Pulendran
The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days. Infants mounted a robust mucosal immune response characterized by inflammatory cytokines, interferon (IFN) α, and T helper (Th) 17 and neutrophil markers (interleukin [IL]-17, IL-8, and CXCL1)...
September 26, 2023: Cell
Roeltje R Maas, Klara Soukup, Nadine Fournier, Matteo Massara, Sabine Galland, Mara Kornete, Vladimir Wischnewski, Joao Lourenco, Davide Croci, Ángel F Álvarez-Prado, Damien N Marie, Johanna Lilja, Rachel Marcone, Gabriel F Calvo, Rui Santalla Mendez, Pauline Aubel, Leire Bejarano, Pratyaksha Wirapati, Iván Ballesteros, Andrés Hidalgo, Andreas F Hottinger, Jean-Philippe Brouland, Roy T Daniel, Monika E Hegi, Johanna A Joyce
Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors in substantial numbers. However, their precise functions in different cancer types remain incompletely understood, including in the brain microenvironment. We therefore investigated neutrophils in tumor tissue of glioma and brain metastasis patients, with matched peripheral blood, and herein describe the first in-depth analysis of neutrophil phenotypes and functions in these tissues. Orthogonal profiling strategies in humans and mice revealed that brain tumor-associated neutrophils (TANs) differ significantly from blood neutrophils and have a prolonged lifespan and immune-suppressive and pro-angiogenic capacity...
September 23, 2023: Cell
Tomohiro Hino, Satoshi N Omura, Ryoya Nakagawa, Tomoki Togashi, Satoru N Takeda, Takafumi Hiramoto, Satoshi Tasaka, Hisato Hirano, Takeshi Tokuyama, Hideki Uosaki, Soh Ishiguro, Madina Kagieva, Hiroyuki Yamano, Yuki Ozaki, Daisuke Motooka, Hideto Mori, Yuhei Kirita, Yoshiaki Kise, Yuzuru Itoh, Satoaki Matoba, Hiroyuki Aburatani, Nozomu Yachie, Tautvydas Karvelis, Virginijus Siksnys, Tsukasa Ohmori, Atsushi Hoshino, Osamu Nureki
SpCas9 and AsCas12a are widely utilized as genome-editing tools in human cells. However, their relatively large size poses a limitation for delivery by cargo-size-limited adeno-associated virus (AAV) vectors. The type V-F Cas12f from Acidibacillus sulfuroxidans is exceptionally compact (422 amino acids) and has been harnessed as a compact genome-editing tool. Here, we developed an approach, combining deep mutational scanning and structure-informed design, to successfully generate two AsCas12f activity-enhanced (enAsCas12f) variants...
September 22, 2023: Cell
Joseph L Watson, Lara K Krüger, Ariel J Ben-Sasson, Alice Bittleston, Marta N Shahbazi, Vicente Jose Planelles-Herrero, Joseph E Chambers, James D Manton, David Baker, Emmanuel Derivery
Polarized cells rely on a polarized cytoskeleton to function. Yet, how cortical polarity cues induce cytoskeleton polarization remains elusive. Here, we capitalized on recently established designed 2D protein arrays to ectopically engineer cortical polarity of virtually any protein of interest during mitosis in various cell types. This enables direct manipulation of polarity signaling and the identification of the cortical cues sufficient for cytoskeleton polarization. Using this assay, we dissected the logic of the Par complex pathway, a key regulator of cytoskeleton polarity during asymmetric cell division...
September 20, 2023: Cell
Shanhe Yu, Yingni Lin, Yong Li, Shijun Chen, Lina Zhou, Hejie Song, Cuiping Yang, Haiqing Zhang, Jianping Zhou, Shunchang Sun, Yanan Li, Juan Chen, Ruixue Feng, Niu Qiao, Yinyin Xie, Ruihong Zhang, Tong Yin, Saijuan Chen, Qingyun Li, Jiang Zhu, Jieming Qu
SARS-CoV-2 primary strain-based vaccination exerts a protective effect against Omicron variants-initiated infection, symptom occurrence, and disease severity in a booster-dependent manner. Yet, the underlying mechanisms remain unclear. During the 2022 Omicron outbreak in Shanghai, we enrolled 122 infected adults and 50 uninfected controls who had been unvaccinated or vaccinated with two or three doses of COVID-19 inactive vaccines and performed integrative analysis of 41-plex CyTOF, RNA-seq, and Olink on their peripheral blood samples...
September 20, 2023: Cell
Daniel S Malawsky, Eva van Walree, Benjamin M Jacobs, Teng Hiang Heng, Qin Qin Huang, Ataf H Sabir, Saadia Rahman, Saghira Malik Sharif, Ahsan Khan, Maša Umićević Mirkov, Hiroyuki Kuwahara, Xin Gao, Fowzan S Alkuraya, Danielle Posthuma, William G Newman, Christopher J Griffiths, Rohini Mathur, David A van Heel, Sarah Finer, Jared O'Connell, Hilary C Martin
Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (FROH ) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of FROH . Within this group in G&H+UK Biobank, we found experiment-wide significant associations between FROH and twelve common diseases...
September 20, 2023: Cell
Jiayue Chen, Renbo Yu, Na Li, Zhaoguo Deng, Xinxin Zhang, Yaran Zhao, Chengfu Qu, Yanfang Yuan, Zhexian Pan, Yangyang Zhou, Kunlun Li, Jiajun Wang, Zhiren Chen, Xiaoyi Wang, Xiaolian Wang, Shu-Nan He, Juan Dong, Xing Wang Deng, Haodong Chen
Gravity controls directional growth of plants, and the classical starch-statolith hypothesis proposed more than a century ago postulates that amyloplast sedimentation in specialized cells initiates gravity sensing, but the molecular mechanism remains uncharacterized. The LAZY proteins are known as key regulators of gravitropism, and lazy mutants show striking gravitropic defects. Here, we report that gravistimulation by reorientation triggers mitogen-activated protein kinase (MAPK) signaling-mediated phosphorylation of Arabidopsis LAZY proteins basally polarized in root columella cells...
September 20, 2023: Cell
Mehdi Bouhaddou, Ann-Kathrin Reuschl, Benjamin J Polacco, Lucy G Thorne, Manisha R Ummadi, Chengjin Ye, Romel Rosales, Adrian Pelin, Jyoti Batra, Gwendolyn M Jang, Jiewei Xu, Jack M Moen, Alicia L Richards, Yuan Zhou, Bhavya Harjai, Erica Stevenson, Ajda Rojc, Roberta Ragazzini, Matthew V X Whelan, Wilhelm Furnon, Giuditta De Lorenzo, Vanessa Cowton, Abdullah M Syed, Alison Ciling, Noa Deutsch, Daniel Pirak, Giulia Dowgier, Dejan Mesner, Jane L Turner, Briana L McGovern, M Luis Rodriguez, Rocio Leiva-Rebollo, Alistair S Dunham, Xiaofang Zhong, Manon Eckhardt, Andrea Fossati, Nicholas F Liotta, Thomas Kehrer, Anastasija Cupic, Magdalena Rutkowska, Ignacio Mena, Sadaf Aslam, Alyssa Hoffert, Helene Foussard, Charles Ochieng' Olwal, Weiqing Huang, Thomas Zwaka, John Pham, Molly Lyons, Laura Donohue, Aliesha Griffin, Rebecca Nugent, Kevin Holden, Robert Deans, Pablo Aviles, Jose A Lopez-Martin, Jose M Jimeno, Kirsten Obernier, Jacqueline M Fabius, Margaret Soucheray, Ruth Hüttenhain, Irwin Jungreis, Manolis Kellis, Ignacia Echeverria, Kliment Verba, Paola Bonfanti, Pedro Beltrao, Roded Sharan, Jennifer A Doudna, Luis Martinez-Sobrido, Arvind H Patel, Massimo Palmarini, Lisa Miorin, Kris White, Danielle L Swaney, Adolfo Garcia-Sastre, Clare Jolly, Lorena Zuliani-Alvarez, Greg J Towers, Nevan J Krogan
SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA...
September 19, 2023: Cell
Mathias Jucker, Lary C Walker
Recent Aβ-immunotherapy trials have yielded the first clear evidence that removing aggregated Aβ from the brains of symptomatic patients can slow the progression of Alzheimer's disease. The clinical benefit achieved in these trials has been modest, however, highlighting the need for both a deeper understanding of disease mechanisms and the importance of intervening early in the pathogenic cascade. An immunoprevention strategy for Alzheimer's disease is required that will integrate the findings from clinical trials with mechanistic insights from preclinical disease models to select promising antibodies, optimize the timing of intervention, identify early biomarkers, and mitigate potential side effects...
September 17, 2023: Cell
Yan-Mei Chen, Shu-Jian Hu, Xian-Dan Lin, Jun-Hua Tian, Jia-Xin Lv, Miao-Ruo Wang, Xiu-Qi Luo, Yuan-Yuan Pei, Rui-Xue Hu, Zhi-Gang Song, Edward C Holmes, Yong-Zhen Zhang
Bats, rodents, and shrews are the most important animal sources of human infectious diseases. However, the evolution and transmission of viruses among them remain largely unexplored. Through the meta-transcriptomic sequencing of internal organ and fecal samples from 2,443 wild bats, rodents, and shrews sampled from four Chinese habitats, we identified 669 viruses, including 534 novel viruses, thereby greatly expanding the mammalian virome. Our analysis revealed high levels of phylogenetic diversity, identified cross-species virus transmission events, elucidated virus origins, and identified cases of invertebrate viruses in mammalian hosts...
September 14, 2023: Cell
Sebastián R Najle, Xavier Grau-Bové, Anamaria Elek, Cristina Navarrete, Damiano Cianferoni, Cristina Chiva, Didac Cañas-Armenteros, Arrate Mallabiabarrena, Kai Kamm, Eduard Sabidó, Harald Gruber-Vodicka, Bernd Schierwater, Luis Serrano, Arnau Sebé-Pedrós
The assembly of the neuronal and other major cell type programs occurred early in animal evolution. We can reconstruct this process by studying non-bilaterians like placozoans. These small disc-shaped animals not only have nine morphologically described cell types and no neurons but also show coordinated behaviors triggered by peptide-secreting cells. We investigated possible neuronal affinities of these peptidergic cells using phylogenetics, chromatin profiling, and comparative single-cell genomics in four placozoans...
September 14, 2023: Cell
Malika Aid, Michaela Sciacca, Katherine McMahan, David Hope, Jinyan Liu, Catherine Jacob-Dolan, Olivia Powers, Julia Barrett, Cindy Wu, Audrey Mutoni, Tetyana Murdza, Hannah Richter, Jason Velasco, Elyse Teow, Mona Boursiquot, Anthony Cook, Tatyana Orekov, Melissa Hamilton, Laurent Pessaint, Alaina Ryan, Tammy Hayes, Amanda J Martinot, Michael S Seaman, Mark G Lewis, Hanne Andersen, Dan H Barouch
The mpox outbreak of 2022-2023 involved rapid global spread in men who have sex with men. We infected 18 rhesus macaques with mpox by the intravenous, intradermal, and intrarectal routes and observed robust antibody and T cell responses following all three routes of infection. Numerous skin lesions and high plasma viral loads were observed following intravenous and intradermal infection. Skin lesions peaked on day 10 and resolved by day 28 following infection. On day 28, we re-challenged all convalescent and 3 naive animals with mpox...
September 13, 2023: Cell
Shouxiong Huang, Adam Shahine, Tan-Yun Cheng, Yi-Ling Chen, Soo Weei Ng, Gautham R Balaji, Rachel Farquhar, Stephanie Gras, Clare S Hardman, John D Altman, Nabil Tahiri, Adriaan J Minnaard, Graham S Ogg, Jacob A Mayfield, Jamie Rossjohn, D Branch Moody
The CD1 system binds lipid antigens for display to T cells. Here, we solved lipidomes for the four human CD1 antigen-presenting molecules, providing a map of self-lipid display. Answering a basic question, the detection of >2,000 CD1-lipid complexes demonstrates broad presentation of self-sphingolipids and phospholipids. Whereas peptide antigens are chemically processed, many lipids are presented in an unaltered form. However, each type of CD1 protein differentially edits the self-lipidome to show distinct capture motifs based on lipid length and chemical composition, suggesting general antigen display mechanisms...
September 12, 2023: Cell
Andrés H Cardona, Szilvia Ecsedi, Mokrane Khier, Zhou Yi, Alia Bahri, Amira Ouertani, Florian Valero, Margaux Labrosse, Sami Rouquet, Stéphane Robert, Agnès Loubat, Danielle Adekunle, Arnaud Hubstenberger
Cellular homeostasis requires the robust control of biomolecule concentrations, but how do millions of mRNAs coordinate their stoichiometries in the face of dynamic translational changes? Here, we identified a two-tiered mechanism controlling mRNA:mRNA and mRNA:protein stoichiometries where mRNAs super-assemble into condensates with buffering capacity and sorting selectivity through phase-transition mechanisms. Using C. elegans oogenesis arrest as a model, we investigated the transcriptome cytosolic reorganization through the sequencing of RNA super-assemblies coupled with single mRNA imaging...
September 28, 2023: Cell
Min Yang, Jennie Ong, Fanju Meng, Feixiang Zhang, Hui Shen, Kerstin Kitt, Tengfei Liu, Wei Tao, Peng Du
Endometrial decidualization connecting embryo implantation and placentation is transient but essential for successful pregnancy, which, however, is not systematically investigated. Here, we use a scStereo-seq technology to spatially visualize and define the dynamic functional decidual hubs assembled by distinct immune, endothelial, trophoblast, and decidual stromal cells (DSCs) in early pregnant mice. We unravel the DSC transdifferentiation trajectory and surprisingly discover a dual-featured type of immune-featured DSCs (iDSCs)...
September 7, 2023: Cell
Zeshuai Wang, Zhisheng Wu, Hao Wang, Ruoqing Feng, Guanlin Wang, Muxi Li, Shuang-Yin Wang, Xiaoyan Chen, Yiyi Su, Jun Wang, Weiwen Zhang, Yuzhou Bao, Zhenwei Lan, Zhuo Song, Yiheng Wang, Xianyang Luo, Lingyu Zhao, Anli Hou, Shuye Tian, Hongliang Gao, Wenbin Miao, Yingyu Liu, Huilin Wang, Cui Yin, Zhi-Liang Ji, Mingqian Feng, Hongkun Liu, Lianghui Diao, Ido Amit, Yun Chen, Yong Zeng, Florent Ginhoux, Xueqing Wu, Yuanfang Zhu, Hanjie Li
Macrophages are heterogeneous and play critical roles in development and disease, but their diversity, function, and specification remain inadequately understood during human development. We generated a single-cell RNA sequencing map of the dynamics of human macrophage specification from PCW 4-26 across 19 tissues. We identified a microglia-like population and a proangiogenic population in 15 macrophage subtypes. Microglia-like cells, molecularly and morphologically similar to microglia in the CNS, are present in the fetal epidermis, testicle, and heart...
September 6, 2023: Cell
Susan R Davis, JoAnn Pinkerton, Nanette Santoro, Tommaso Simoncini
Menopause is the cessation of ovarian function, with loss of reproductive hormone production and irreversible loss of fertility. It is a natural part of reproductive aging. The physiology of the menopause is complex and incompletely understood. Globally, menopause occurs around the age of 49 years, with geographic and ethnic variation. The hormonal changes of the menopause transition may result in both symptoms and long-term systemic effects, predominantly adverse effects on cardiometabolic and musculoskeletal health...
September 5, 2023: Cell
Yaxi Wang, Larry A Gallagher, Pia A Andrade, Andi Liu, Ian R Humphreys, Serdar Turkarslan, Kevin J Cutler, Mario L Arrieta-Ortiz, Yaqiao Li, Matthew C Radey, Jeffrey S McLean, Qian Cong, David Baker, Nitin S Baliga, S Brook Peterson, Joseph D Mougous
Patescibacteria, also known as the candidate phyla radiation (CPR), are a diverse group of bacteria that constitute a disproportionately large fraction of microbial dark matter. Its few cultivated members, belonging mostly to Saccharibacteria, grow as epibionts on host Actinobacteria. Due to a lack of suitable tools, the genetic basis of this lifestyle and other unique features of Patescibacteira remain unexplored. Here, we show that Saccharibacteria exhibit natural competence, and we exploit this property for their genetic manipulation...
August 30, 2023: Cell
Kyonsoo Hong, Lindsay Hinck, Makoto Nishiyama, Mu-Ming Poo, Marc Tessier-Lavigne, Elke Stein
No abstract text is available yet for this article.
August 30, 2023: Cell
Seiya Tajima, Yoon Seok Kim, Masahiro Fukuda, YoungJu Jo, Peter Y Wang, Joseph M Paggi, Masatoshi Inoue, Eamon F X Byrne, Koichiro E Kishi, Seiwa Nakamura, Charu Ramakrishnan, Shunki Takaramoto, Takashi Nagata, Masae Konno, Masahiro Sugiura, Kota Katayama, Toshiki E Matsui, Keitaro Yamashita, Suhyang Kim, Hisako Ikeda, Jaeah Kim, Hideki Kandori, Ron O Dror, Keiichi Inoue, Karl Deisseroth, Hideaki E Kato
KCR channelrhodopsins (K+ -selective light-gated ion channels) have received attention as potential inhibitory optogenetic tools but more broadly pose a fundamental mystery regarding how their K+ selectivity is achieved. Here, we present 2.5-2.7 Å cryo-electron microscopy structures of HcKCR1 and HcKCR2 and of a structure-guided mutant with enhanced K+ selectivity. Structural, electrophysiological, computational, spectroscopic, and biochemical analyses reveal a distinctive mechanism for K+ selectivity; rather than forming the symmetrical filter of canonical K+ channels achieving both selectivity and dehydration, instead, three extracellular-vestibule residues within each monomer form a flexible asymmetric selectivity gate, while a distinct dehydration pathway extends intracellularly...
August 30, 2023: Cell
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