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JOURNAL ARTICLE
Philip Francis Thomsen, Mads Reinholdt Jensen, Eva Egelyng Sigsgaard
Environmental DNA (eDNA) has opened promising avenues for establishing standardized, cost-efficient monitoring of biodiversity. However, comprehensive and systematic implementation is urgently needed to address the current biodiversity crisis. Here, we envision a global eDNA biomonitoring scheme, which could potentially revolutionize the understanding and conservation of life on Earth.
May 9, 2024: Cell
#2
JOURNAL ARTICLE
ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity.
Matthew B Maxwell, Marianne S Hom-Tedla, Jawoon Yi, Shitian Li, Samuel A Rivera, Jingting Yu, Mannix J Burns, Helen M McRae, Braden T Stevenson, Katherine E Coakley, Josephine Ho, Kameneff Bojorquez Gastelum, Joshua C Bell, Alexander C Jones, Ramez N Eskander, Emily C Dykhuizen, Gerald S Shadel, Susan M Kaech, Diana C Hargreaves
Clinical trials have identified ARID1A mutations as enriched among patients who respond favorably to immune checkpoint blockade (ICB) in several solid tumor types independent of microsatellite instability. We show that ARID1A loss in murine models is sufficient to induce anti-tumor immune phenotypes observed in ARID1A mutant human cancers, including increased CD8+ T cell infiltration and cytolytic activity. ARID1A-deficient cancers upregulated an interferon (IFN) gene expression signature, the ARID1A-IFN signature, associated with increased R-loops and cytosolic single-stranded DNA (ssDNA)...
May 9, 2024: Cell
#3
JOURNAL ARTICLE
Sergi Junyent, Maciej Meglicki, Roman Vetter, Rachel Mandelbaum, Catherine King, Ekta M Patel, Lisa Iwamoto-Stohl, Clare Reynell, Dong-Yuan Chen, Patrizia Rubino, Nabil Arrach, Richard J Paulson, Dagmar Iber, Magdalena Zernicka-Goetz
Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo...
May 9, 2024: Cell
#4
JOURNAL ARTICLE
Jinjia Zhang, Junhong Li, Yongqiang Hou, Yao Lin, Hao Zhao, Yiran Shi, Kaiyun Chen, Cheng Nian, Jiayu Tang, Lei Pan, Yunzhi Xing, Huan Gao, Bingying Yang, Zengfang Song, Yao Cheng, Yue Liu, Min Sun, Yueyue Linghu, Jiaxin Li, Haitao Huang, Zhangjian Lai, Zhien Zhou, Zifeng Li, Xiufeng Sun, Qinghua Chen, Dongxue Su, Wengang Li, Zhihai Peng, Pingguo Liu, Wei Chen, Hongling Huang, Yixin Chen, Bailong Xiao, Lilin Ye, Lanfen Chen, Dawang Zhou
Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis...
May 9, 2024: Cell
#5
JOURNAL ARTICLE
Rebecca A Green, Renat N Khaliullin, Zhiling Zhao, Stacy D Ochoa, Jeffrey M Hendel, Tiffany-Lynn Chow, HongKee Moon, Ronald J Biggs, Arshad Desai, Karen Oegema
Systematic functional profiling of the gene set that directs embryonic development is an important challenge. To tackle this challenge, we used 4D imaging of C. elegans embryogenesis to capture the effects of 500 gene knockdowns and developed an automated approach to compare developmental phenotypes. The automated approach quantifies features-including germ layer cell numbers, tissue position, and tissue shape-to generate temporal curves whose parameterization yields numerical phenotypic signatures. In conjunction with a new similarity metric that operates across phenotypic space, these signatures enabled the generation of ranked lists of genes predicted to have similar functions, accessible in the PhenoBank web portal, for ∼25% of essential development genes...
May 8, 2024: Cell
#6
JOURNAL ARTICLE
Donna M Poscablo, Atesh K Worthington, Stephanie Smith-Berdan, Marcel G E Rommel, Bryce A Manso, Reheman Adili, Lydia Mok, Roman E Reggiardo, Taylor Cool, Raana Mogharrab, Jenna Myers, Steven Dahmen, Paloma Medina, Anna E Beaudin, Scott W Boyer, Michael Holinstat, Vanessa D Jonsson, E Camilla Forsberg
Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is progressively propagated upon aging. Remarkably, the aging-enriched platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production. This results in two molecularly and functionally distinct populations of megakaryocyte progenitors...
May 8, 2024: Cell
#7
JOURNAL ARTICLE
Carlos Sacristan, Kumiko Samejima, Lorena Andrade Ruiz, Moonmoon Deb, Maaike L A Lambers, Adam Buckle, Chris A Brackley, Daniel Robertson, Tetsuya Hori, Shaun Webb, Robert Kiewisz, Tristan Bepler, Eloïse van Kwawegen, Patrik Risteski, Kruno Vukušić, Iva M Tolić, Thomas Müller-Reichert, Tatsuo Fukagawa, Nick Gilbert, Davide Marenduzzo, William C Earnshaw, Geert J P L Kops
Centromeres are scaffolds for the assembly of kinetochores that ensure chromosome segregation during cell division. How vertebrate centromeres obtain a three-dimensional structure to accomplish their primary function is unclear. Using super-resolution imaging, capture-C, and polymer modeling, we show that vertebrate centromeres are partitioned by condensins into two subdomains during mitosis. The bipartite structure is found in human, mouse, and chicken cells and is therefore a fundamental feature of vertebrate centromeres...
May 8, 2024: Cell
#8
JOURNAL ARTICLE
Kenichi Toma, Mengya Zhao, Shaobo Zhang, Fei Wang, Hannah K Graham, Jun Zou, Shweta Modgil, Wenhao H Shang, Nicole Y Tsai, Zhishun Cai, Liping Liu, Guiying Hong, Arnold R Kriegstein, Yang Hu, Jakob Körbelin, Ruobing Zhang, Yaping Joyce Liao, Tyson N Kim, Xin Ye, Xin Duan
The vasculature of the central nervous system is a 3D lattice composed of laminar vascular beds interconnected by penetrating vessels. The mechanisms controlling 3D lattice network formation remain largely unknown. Combining viral labeling, genetic marking, and single-cell profiling in the mouse retina, we discovered a perivascular neuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs), directly contacting the vasculature with perisomatic endfeet. Developmental ablation of Fam19a4/Nts-RGCs led to disoriented growth of penetrating vessels near the ganglion cell layer (GCL), leading to a disorganized 3D vascular lattice...
May 6, 2024: Cell
#9
JOURNAL ARTICLE
Zicong Zhang, Junfeng Su, Jing Tang, Leeyup Chung, Jessica C Page, Carla C Winter, Yuchu Liu, Evgenii Kegeles, Sara Conti, Yu Zhang, Jason Biundo, Joshua I Chalif, Charles Y Hua, Zhiyun Yang, Xue Yao, Yang Yang, Shuqiang Chen, Jan M Schwab, Kuan Hong Wang, Chinfei Chen, Michael J Prerau, Zhigang He
Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord...
May 3, 2024: Cell
#10
JOURNAL ARTICLE
Yingpu Yu, Maximilian A Kass, Mengyin Zhang, Noor Youssef, Catherine A Freije, Kelly P Brock, Lauren C Aguado, Leon L Seifert, Sanjana Venkittu, Xupeng Hong, Amir Shlomai, Ype P de Jong, Debora S Marks, Charles M Rice, William M Schneider
Hepatitis B virus (HBV) is a small double-stranded DNA virus that chronically infects 296 million people. Over half of its compact genome encodes proteins in two overlapping reading frames, and during evolution, multiple selective pressures can act on shared nucleotides. This study combines an RNA-based HBV cell culture system with deep mutational scanning (DMS) to uncouple cis- and trans-acting sequence requirements in the HBV genome. The results support a leaky ribosome scanning model for polymerase translation, provide a fitness map of the HBV polymerase at single-nucleotide resolution, and identify conserved prolines adjacent to the HBV polymerase termination codon that stall ribosomes...
May 2, 2024: Cell
#11
JOURNAL ARTICLE
Chen Wang, Qun Zeng, Zeynep Melis Gül, Sisi Wang, Robert Pick, Phil Cheng, Ruben Bill, Yan Wu, Stefan Naulaerts, Coline Barnoud, Pei-Chun Hsueh, Sofie Hedlund Moller, Mara Cenerenti, Mengzhu Sun, Ziyang Su, Stéphane Jemelin, Volodymyr Petrenko, Charna Dibner, Stéphanie Hugues, Camilla Jandus, Zhongwu Li, Olivier Michielin, Ping-Chih Ho, Abhishek D Garg, Federico Simonetta, Mikaël J Pittet, Christoph Scheiermann
The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8+ T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day...
May 2, 2024: Cell
#12
JOURNAL ARTICLE
Shovik Bandyopadhyay, Michael P Duffy, Kyung Jin Ahn, Jonathan H Sussman, Minxing Pang, David Smith, Gwendolyn Duncan, Iris Zhang, Jeffrey Huang, Yulieh Lin, Barbara Xiong, Tamjid Imtiaz, Chia-Hui Chen, Anusha Thadi, Changya Chen, Jason Xu, Melissa Reichart, Zachary Martinez, Caroline Diorio, Chider Chen, Vinodh Pillai, Oraine Snaith, Derek Oldridge, Siddharth Bhattacharyya, Ivan Maillard, Martin Carroll, Charles Nelson, Ling Qin, Kai Tan
Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed co-detection by indexing (CODEX) to spatially profile over 1...
May 2, 2024: Cell
#13
JOURNAL ARTICLE
Mana Momenilandi, Romain Lévy, Steicy Sobrino, Jingwei Li, Chantal Lagresle-Peyrou, Hossein Esmaeilzadeh, Antoine Fayand, Corentin Le Floc'h, Antoine Guérin, Erika Della Mina, Debra Shearer, Ottavia M Delmonte, Ahmad Yatim, Kevin Mulder, Mathieu Mancini, Darawan Rinchai, Adeline Denis, Anna-Lena Neehus, Karla Balogh, Sarah Brendle, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Yoann Seeleuthner, Caroline Deswarte, Boris Bessot, Cassandre Cremades, Marie Materna, Axel Cederholm, Masato Ogishi, Quentin Philippot, Omer Beganovic, Mania Ackermann, Margareta Wuyts, Taushif Khan, Sébastien Fouéré, Florian Herms, Johan Chanal, Boaz Palterer, Julie Bruneau, Thierry J Molina, Stéphanie Leclerc-Mercier, Jean-Luc Prétet, Leila Youssefian, Hassan Vahidnezhad, Nima Parvaneh, Kristl G Claeys, Rik Schrijvers, Marine Luka, Philippe Pérot, Jacques Fourgeaud, Céline Nourrisson, Philippe Poirier, Emmanuelle Jouanguy, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Luigi D Notarangelo, Neil Christensen, Nils Landegren, Laurent Abel, Nico Marr, Emmanuelle Six, David Langlais, Tim Waterboer, Florent Ginhoux, Cindy S Ma, Stuart G Tangye, Isabelle Meyts, Nico Lachmann, Jiafen Hu, Mohammad Shahrooei, Xavier Bossuyt, Jean-Laurent Casanova, Vivien Béziat
FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients' blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all...
May 2, 2024: Cell
#14
Julia Joung, Sai Ma, Tristan Tay, Kathryn R Geiger-Schuller, Paul C Kirchgatterer, Vanessa K Verdine, Baolin Guo, Mario A Arias-Garcia, William E Allen, Ankita Singh, Olena Kuksenko, Omar O Abudayyeh, Jonathan S Gootenberg, Zhanyan Fu, Rhiannon K Macrae, Jason D Buenrostro, Aviv Regev, Feng Zhang
No abstract text is available yet for this article.
May 1, 2024: Cell
#15
JOURNAL ARTICLE
Hector R Mendez-Gomez, Anna DeVries, Paul Castillo, Christina von Roemeling, Sadeem Qdaisat, Brian D Stover, Chao Xie, Frances Weidert, Chong Zhao, Rachel Moor, Ruixuan Liu, Dhruvkumar Soni, Elizabeth Ogando-Rivas, Jonathan Chardon-Robles, James McGuiness, Dingpeng Zhang, Michael C Chung, Christiano Marconi, Stephen Michel, Arnav Barpujari, Gabriel W Jobin, Nagheme Thomas, Xiaojie Ma, Yodarlynis Campaneria, Adam Grippin, Aida Karachi, Derek Li, Bikash Sahay, Leighton Elliott, Timothy P Foster, Kirsten E Coleman, Rowan J Milner, W Gregory Sawyer, John A Ligon, Eugenio Simon, Brian Cleaver, Kristine Wynne, Marcia Hodik, Annette M Molinaro, Juan Guan, Patrick Kellish, Andria Doty, Ji-Hyun Lee, Tara Massini, Jesse L Kresak, Jianping Huang, Eugene I Hwang, Cassie Kline, Sheila Carrera-Justiz, Maryam Rahman, Sebastian Gatica, Sabine Mueller, Michael Prados, Ashley P Ghiaseddin, Natalie L Silver, Duane A Mitchell, Elias J Sayour
Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models...
April 26, 2024: Cell
#16
JOURNAL ARTICLE
Xuezhao Liu, Dazhuan Eric Xin, Xiaowen Zhong, Chuntao Zhao, Zhidan Li, Liguo Zhang, Adam J Dourson, Lindsay Lee, Shreya Mishra, Arman E Bayat, Eva Nicholson, William L Seibel, Bingfang Yan, Joel Mason, Bradley J Turner, David G Gonsalvez, William Ong, Sing Yian Chew, Balaram Ghosh, Sung Ok Yoon, Mei Xin, Zhigang He, Jason Tchieu, Michael Wegner, Klaus-Armin Nave, Robin J M Franklin, Ranjan Dutta, Bruce D Trapp, Ming Hu, Matthew A Smith, Michael P Jankowski, Samantha K Barton, Xuelian He, Q Richard Lu
Remyelination failure in diseases like multiple sclerosis (MS) was thought to involve suppressed maturation of oligodendrocyte precursors; however, oligodendrocytes are present in MS lesions yet lack myelin production. We found that oligodendrocytes in the lesions are epigenetically silenced. Developing a transgenic reporter labeling differentiated oligodendrocytes for phenotypic screening, we identified a small-molecule epigenetic-silencing-inhibitor (ESI1) that enhances myelin production and ensheathment...
April 25, 2024: Cell
#17
Thomas Hägglöf, Melissa Cipolla, Maximilian Loewe, Spencer T Chen, Ervin E Kara, Luka Mesin, Harald Hartweger, Mohamed A ElTanbouly, Alice Cho, Anna Gazumyan, Victor Ramos, Leonidas Stamatatos, Thiago Y Oliveira, Michel C Nussenzweig, Charlotte Viant
No abstract text is available yet for this article.
April 23, 2024: Cell
#18
JOURNAL ARTICLE
Yulong Li, Xiangyang Wu, Caibin Sheng, Hailing Liu, Huizhu Liu, Yixuan Tang, Chao Liu, Qingyang Ding, Bin Xie, Xi Xiao, Rongbin Zheng, Quan Yu, Zengdan Guo, Jian Ma, Jin Wang, Jinghong Gao, Mei Tian, Wei Wang, Jia Zhou, Li Jiang, Mengmeng Gu, Sailing Shi, Michael Paull, Guanhua Yang, Wei Yang, Steve Landau, Xingfeng Bao, Xihao Hu, X Shirley Liu, Tengfei Xiao
Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors...
April 18, 2024: Cell
#19
JOURNAL ARTICLE
Zhenyu Xiao, Lina Cui, Yang Yuan, Nannan He, Xinwei Xie, Sirui Lin, Xiaolong Yang, Xin Zhang, Peifu Shi, Zhifeng Wei, Yang Li, Hongmei Wang, Xiaoyan Wang, Yulei Wei, Jingtao Guo, Leqian Yu
Progress in understanding early human development has been impeded by the scarcity of reference datasets from natural embryos, particularly those with spatial information during crucial stages like gastrulation. We conducted high-resolution spatial transcriptomics profiling on 38,562 spots from 62 transverse sections of an intact Carnegie stage (CS) 8 human embryo. From this spatial transcriptomic dataset, we constructed a 3D model of the CS8 embryo, in which a range of cell subtypes are identified, based on gene expression patterns and positional register, along the anterior-posterior, medial-lateral, and dorsal-ventral axis in the embryo...
April 17, 2024: Cell
#20
JOURNAL ARTICLE
Anthony R P Verkerke, Dandan Wang, Naofumi Yoshida, Zachary H Taxin, Xu Shi, Shuning Zheng, Yuka Li, Christopher Auger, Satoshi Oikawa, Jin-Seon Yook, Melia Granath-Panelo, Wentao He, Guo-Fang Zhang, Mami Matsushita, Masayuki Saito, Robert E Gerszten, Evanna L Mills, Alexander S Banks, Yasushi Ishihama, Phillip J White, Robert W McGarrah, Takeshi Yoneshiro, Shingo Kajimura
Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is protective against type 2 diabetes, independent of body weight. The mechanism underlying this dissociation remains unclear. Here, we report that impaired mitochondrial catabolism of branched-chain amino acids (BCAAs) in BAT, by deleting mitochondrial BCAA carriers (MBCs), caused systemic insulin resistance without affecting energy expenditure and body weight...
April 17, 2024: Cell
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