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Cell
This journal offers authors two options (open access or subscription) to publish research

Jun 10, 2021

Volume 184Issue 12p3075-3348
Open Archive
On the cover: Glycans modify lipids and proteins to mediate inter- and intramolecular interactions across all domains of life. RNA is not thought to be a major target of glycosylation. In this issue, Flynn et al. (3109–3124) discover and characterize glycoRNAs comprised of small, structured RNA and N-glycans containing sialic acids on their termini. These findings help expand the scope of RNA biology to the cell surface. The cover image illustrates molecular features of a cell surface presenting many types of glycoconjugates including glycoproteins, glycolipids, and glycoRNAs. Image credit: Emily M. Eng (15219 NE 6th Pl., Bellevue, WA 98007, (206) 949-4393, em@emilymeng.com)....
On the cover: Glycans modify lipids and proteins to mediate inter- and intramolecular interactions across all domains of life. RNA is not thought to be a major target of glycosylation. In this issue, Flynn et al. (3109–3124) discover and characterize glycoRNAs comprised of small, structured RNA and N-glycans containing sialic acids on their termini. These findings help expand the scope of RNA biology to the cell surface. The cover image illustrates molecular features of a cell surface presenting many types of glycoconjugates including glycoproteins, glycolipids, and glycoRNAs. Image credit: Emily M. Eng (15219 NE 6th Pl., Bellevue, WA 98007, (206) 949-4393, em@emilymeng.com).

Leading Edge

Commentary

  • Affirming NIH’s commitment to addressing structural racism in the biomedical research enterprise

    • Francis S. Collins,
    • Amy Bany Adams,
    • Courtney Aklin,
    • Trevor K. Archer,
    • Marie A. Bernard,
    • Ericka Boone,
    • John Burklow,
    • Michele K. Evans,
    • Sadhana Jackson,
    • Alfred C. Johnson,
    • Jon Lorsch,
    • Mia Rochelle Lowden,
    • Anna María Nápoles,
    • Anna E. Ordóñez,
    • Robert Rivers,
    • Victoria Rucker,
    • Tara Schwetz,
    • Julia A. Segre,
    • Lawrence A. Tabak,
    • Monica Webb Hooper,
    • Carrie Wolinetz
    • NIH UNITE
    NIH has acknowledged and committed to ending structural racism. The framework for NIH’s approach, summarized here, includes understanding barriers; developing robust health disparities/equity research; improving its internal culture; being transparent and accountable; and changing the extramural ecosystem so that diversity, equity, and inclusion are reflected in funded research and the biomedical workforce.

Previews

  • A glimpse at the glycoRNA world

    • Matthew D. Disney
    In the past several decades, there has been an increased appreciation of RNA modifications and their biological functions. In this issue of Cell, Flynn et al. describe the discovery of glycoRNAs present on the surface of cells. Like proteins and lipids, conserved non-coding RNAs are functionalized with carbohydrates.
  • Death in the Fas, ELANE

    • Anthony Letai
    In this issue of Cell, Cui et al. demonstrate a previously unknown capacity for neutrophils to selectively kill cancer cells. How this killing is effected unfolds as a story of classical biochemistry, novel cell biology, and innate and adaptive immunity.
  • Seq-ing out cell types across the isocortex and hippocampal formation

    • Guo-li Ming,
    • Hongjun Song
    A central quest in neuroscience is to gain a holistic understanding of all cell types in the brain. In this issue of Cell, Yao et al. establish a molecular architectural view of cell types across the entire adult mouse isocortex and hippocampal formation and reveal surprising similarities of cell types in these two brain regions.

Review

Articles

  • Small RNAs are modified with N-glycans and displayed on the surface of living cells

    • Ryan A. Flynn,
    • Kayvon Pedram,
    • Stacy A. Malaker,
    • Pedro J. Batista,
    • Benjamin A.H. Smith,
    • Alex G. Johnson,
    • Benson M. George,
    • Karim Majzoub,
    • Peter W. Villalta,
    • Jan E. Carette,
    • Carolyn R. Bertozzi
    Identification of stable mammalian RNAs decorated with glycan structures opens up a new dimension for regulatory control of RNA localization and function by post-transcriptional modification.
  • Splice site m6A methylation prevents binding of U2AF35 to inhibit RNA splicing

    • Mateusz Mendel,
    • Kamila Delaney,
    • Radha Raman Pandey,
    • Kuan-Ming Chen,
    • Joanna M. Wenda,
    • Cathrine Broberg Vågbø,
    • Florian A. Steiner,
    • David Homolka,
    • Ramesh S. Pillai
    m6A methylation of a 3ʹ splice site blocks its recognition by splicing factors to inhibit pre-mRNA splicing in nematodes and mammals. In worms, this mechanism is used to modulate splicing in response to a change in diet.
  • The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer

    • Stephin J. Vervoort,
    • Sarah A. Welsh,
    • Jennifer R. Devlin,
    • Elisa Barbieri,
    • Deborah A. Knight,
    • Sarah Offley,
    • Stefan Bjelosevic,
    • Matteo Costacurta,
    • Izabela Todorovski,
    • Conor J. Kearney,
    • Jarrod J. Sandow,
    • Zheng Fan,
    • Benjamin Blyth,
    • Victoria McLeod,
    • Joseph H.A. Vissers,
    • Karolina Pavic,
    • Ben P. Martin,
    • Gareth Gregory,
    • Elena Demosthenous,
    • Magnus Zethoven,
    • Isabella Y. Kong,
    • Edwin D. Hawkins,
    • Simon J. Hogg,
    • Madison J. Kelly,
    • Andrea Newbold,
    • Kaylene J. Simpson,
    • Otto Kauko,
    • Kieran F. Harvey,
    • Michael Ohlmeyer,
    • Jukka Westermarck,
    • Nathanael Gray,
    • Alessandro Gardini,
    • Ricky W. Johnstone
    Interplay between PP2A and CDK9 provides a control point for gene expression that can be exploited to inhibit tumorigenesis.
  • Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis

    • Chang Cui,
    • Kasturi Chakraborty,
    • Xu Anna Tang,
    • Guolin Zhou,
    • Kelly Q. Schoenfelt,
    • Kristen M. Becker,
    • Alexandria Hoffman,
    • Ya-Fang Chang,
    • Ariane Blank,
    • Catherine A. Reardon,
    • Hilary A. Kenny,
    • Tomas Vaisar,
    • Ernst Lengyel,
    • Geoffrey Greene,
    • Lev Becker
    Neutrophil-secreted elastase shows dramatic selectivity, inducing cell death in tumors and at metastatic sites in animal models while sparing proximal healthy cells.
  • Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions

    • Justin M. Hansen,
    • Maarten F. de Jong,
    • Qi Wu,
    • Li-Shu Zhang,
    • David B. Heisler,
    • Laura T. Alto,
    • Neal M. Alto
    Repurposing a cell death mechanism for antibacterial defense, human immune cells combat infection by punching holes in bacterial membranes. A human pathogen has evolved a way to fight back.
  • Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia

    • Daniel Asarnow,
    • Bei Wang,
    • Wen-Hsin Lee,
    • Yuanyu Hu,
    • Ching-Wen Huang,
    • Bryan Faust,
    • Patricia Miang Lon Ng,
    • Eve Zi Xian Ngoh,
    • Markus Bohn,
    • David Bulkley,
    • Andrés Pizzorno,
    • Beatrice Ary,
    • Hwee Ching Tan,
    • Chia Yin Lee,
    • Rabiatul Adawiyah Minhat,
    • Olivier Terrier,
    • Mun Kuen Soh,
    • Frannie Jiuyi Teo,
    • Yvonne Yee Chin Yeap,
    • Shirley Gek Kheng Seah,
    • Conrad En Zuo Chan,
    • Emily Connelly,
    • Nicholas J. Young,
    • Sebastian Maurer-Stroh,
    • Laurent Renia,
    • Brendon John Hanson,
    • Manuel Rosa-Calatrava,
    • Aashish Manglik,
    • Yifan Cheng,
    • Charles S. Craik,
    • Cheng-I Wang
    A series of antibodies against SARS-CoV-2 that potently block binding to the host receptor ACE2 are found to enhance or inhibit virus Spike-mediated membrane fusion and formation of syncytia, a sign of tissue damage in individuals with COVID-19.
  • B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV

    • Johannes F. Scheid,
    • Christopher O. Barnes,
    • Basak Eraslan,
    • Andrew Hudak,
    • Jennifer R. Keeffe,
    • Lisa A. Cosimi,
    • Eric M. Brown,
    • Frauke Muecksch,
    • Yiska Weisblum,
    • Shuting Zhang,
    • Toni Delorey,
    • Ann E. Woolley,
    • Fadi Ghantous,
    • Sung-Moo Park,
    • Devan Phillips,
    • Betsabeh Tusi,
    • Kathryn E. Huey-Tubman,
    • Alexander A. Cohen,
    • Priyanthi N.P. Gnanapragasam,
    • Kara Rzasa,
    • Theodora Hatziioanno,
    • Michael A. Durney,
    • Xiebin Gu,
    • Takuya Tada,
    • Nathaniel R. Landau,
    • Anthony P. West Jr.,
    • Orit Rozenblatt-Rosen,
    • Michael S. Seaman,
    • Lindsey R. Baden,
    • Daniel B. Graham,
    • Jacques Deguine,
    • Paul D. Bieniasz,
    • Aviv Regev,
    • Deborah Hung,
    • Pamela J. Bjorkman,
    • Ramnik J. Xavier
    B cell genomics reveals transcriptionally distinct populations that modulate antibody responses to SARS-CoV-2, with the identification of a monoclonal antibody that locks the virus spike trimer to neutralize recent variants, SARS and heterologous RBDs.
  • A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

    • Zizhen Yao,
    • Cindy T.J. van Velthoven,
    • Thuc Nghi Nguyen,
    • Jeff Goldy,
    • Adriana E. Sedeno-Cortes,
    • Fahimeh Baftizadeh,
    • Darren Bertagnolli,
    • Tamara Casper,
    • Megan Chiang,
    • Kirsten Crichton,
    • Song-Lin Ding,
    • Olivia Fong,
    • Emma Garren,
    • Alexandra Glandon,
    • Nathan W. Gouwens,
    • James Gray,
    • Lucas T. Graybuck,
    • Michael J. Hawrylycz,
    • Daniel Hirschstein,
    • Matthew Kroll,
    • Kanan Lathia,
    • Changkyu Lee,
    • Boaz Levi,
    • Delissa McMillen,
    • Stephanie Mok,
    • Thanh Pham,
    • Qingzhong Ren,
    • Christine Rimorin,
    • Nadiya Shapovalova,
    • Josef Sulc,
    • Susan M. Sunkin,
    • Michael Tieu,
    • Amy Torkelson,
    • Herman Tung,
    • Katelyn Ward,
    • Nick Dee,
    • Kimberly A. Smith,
    • Bosiljka Tasic,
    • Hongkui Zeng
    Single-cell transcriptomics of the entire mouse isocortex and hippocampal formation shows shared cellular and circuit organization and large-scale continuous gradients of neuron-type variation that illuminates the underlying relationship between these two critical brain structures.
  • Phase precession in the human hippocampus and entorhinal cortex

    • Salman E. Qasim,
    • Itzhak Fried,
    • Joshua Jacobs
    Neurons in the human brain spike in rhythm with local network oscillations to represent spatial position and non-spatial states, highlighting phase procession as a widespread neuronal mechanism for coordinating spike timing during behavior and cognition.
  • The deep population history of northern East Asia from the Late Pleistocene to the Holocene

    • Xiaowei Mao,
    • Hucai Zhang,
    • Shiyu Qiao,
    • Yichen Liu,
    • Fengqin Chang,
    • Ping Xie,
    • Ming Zhang,
    • Tianyi Wang,
    • Mian Li,
    • Peng Cao,
    • Ruowei Yang,
    • Feng Liu,
    • Qingyan Dai,
    • Xiaotian Feng,
    • Wanjing Ping,
    • Chuzhao Lei,
    • John W. Olsen,
    • E. Andrew Bennett,
    • Qiaomei Fu
    Mao et al. demonstrate that the ancestry of the ca. 40 ka individual from Tianyuan Cave near Beijing was widespread geographically and temporally before the Last Glacial Maximum (LGM; ca. 26.5–19 ka). At the end of the LGM, the earliest northern East Asian appeared. After 14 ka, populations in the Amur region comprised the closest East Asian source known for Ancient Paleo-Siberians. Among adaptive genetic variants, EDAR V370A was likely to have been elevated to high frequency after the LGM.
  • Efficient embryonic homozygous gene conversion via RAD51-enhanced interhomolog repair

    • Jonathan J. Wilde,
    • Tomomi Aida,
    • Ricardo C.H. del Rosario,
    • Tobias Kaiser,
    • Peimin Qi,
    • Martin Wienisch,
    • Qiangge Zhang,
    • Steven Colvin,
    • Guoping Feng
    Co-injection of mouse zygotes with RAD51 and Cas9 can enhance interhomolog repair and facilitate conversion of heterozygous alleles to homozygous alleles.

Resources

  • Charting human development using a multi-endodermal organ atlas and organoid models

    • Qianhui Yu,
    • Umut Kilik,
    • Emily M. Holloway,
    • Yu-Hwai Tsai,
    • Christoph Harmel,
    • Angeline Wu,
    • Joshua H. Wu,
    • Michael Czerwinski,
    • Charlie J. Childs,
    • Zhisong He,
    • Meghan M. Capeling,
    • Sha Huang,
    • Ian A. Glass,
    • Peter D.R. Higgins,
    • Barbara Treutlein,
    • Jason R. Spence,
    • J. Gray Camp
    A reference atlas of multiple human developing endodermal organs of the respiratory and gastrointestinal tract is described and used to provide information regarding cell states, transcription factors, and organ-specific epithelial stem cell and mesenchyme interactions across lineages as well as benchmark stem cell-derived human intestinal organoids under multiple culture conditions.
  • Cardioids reveal self-organizing principles of human cardiogenesis

    • Pablo Hofbauer,
    • Stefan M. Jahnel,
    • Nora Papai,
    • Magdalena Giesshammer,
    • Alison Deyett,
    • Clara Schmidt,
    • Mirjam Penc,
    • Katherina Tavernini,
    • Nastasja Grdseloff,
    • Christy Meledeth,
    • Lavinia Ceci Ginistrelli,
    • Claudia Ctortecka,
    • Šejla Šalic,
    • Maria Novatchkova,
    • Sasha Mendjan
    Cardioids that pattern and morph into chamber-like structures are established from human pluripotent stem cells.
  • Iterative tomography with digital adaptive optics permits hour-long intravital observation of 3D subcellular dynamics at millisecond scale

    • Jiamin Wu,
    • Zhi Lu,
    • Dong Jiang,
    • Yuduo Guo,
    • Hui Qiao,
    • Yi Zhang,
    • Tianyi Zhu,
    • Yeyi Cai,
    • Xu Zhang,
    • Karl Zhanghao,
    • Hao Xie,
    • Tao Yan,
    • Guoxun Zhang,
    • Xiaoxu Li,
    • Zheng Jiang,
    • Xing Lin,
    • Lu Fang,
    • Bing Zhou,
    • Peng Xi,
    • Jingtao Fan,
    • Li Yu,
    • Qionghai Dai
    Ultrahigh-resolution fluorescence imaging with low phototoxicity enables 3D visualization of fast cellular and subcellular processes in organoids, zebrafish, and mammals.
  • Innovation, conservation, and repurposing of gene function in root cell type development

    • Kaisa Kajala,
    • Mona Gouran,
    • Lidor Shaar-Moshe,
    • G. Alex Mason,
    • Joel Rodriguez-Medina,
    • Dorota Kawa,
    • Germain Pauluzzi,
    • Mauricio Reynoso,
    • Alex Canto-Pastor,
    • Concepcion Manzano,
    • Vincent Lau,
    • Mariana A.S. Artur,
    • Donnelly A. West,
    • Sharon B. Gray,
    • Alexander T. Borowsky,
    • Bryshal P. Moore,
    • Andrew I. Yao,
    • Kevin W. Morimoto,
    • Marko Bajic,
    • Elide Formentin,
    • Niba A. Nirmal,
    • Alan Rodriguez,
    • Asher Pasha,
    • Roger B. Deal,
    • Daniel J. Kliebenstein,
    • Torgeir R. Hvidsten,
    • Nicholas J. Provart,
    • Neelima R. Sinha,
    • Daniel E. Runcie,
    • Julia Bailey-Serres,
    • Siobhan M. Brady
    The integration of pan-species cell type data reveals molecular signatures across growth conditions and sheds light on novelty, conservation, and repurposing of gene function relevant to crop engineering.
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