Journal ArticleDOI
In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer.
Zeyu Chen,Eri Arai,Omar Khan,Zhen Zhang,Shin Foong Ngiow,Yuan He,Hua Huang,Sasikanth Manne,Zhendong Cao,Amy E. Baxter,Zhangying Cai,Elizabeth Freilich,Mohammed Alkhatim A. Ali,Josephine R. Giles,Jennifer E. Wu,Allison R. Greenplate,Mohamed A. Hakeem,Qingzhou Chen,Makoto Kurachi,Kito Nzingha,Viktoriya Ekshyyan,Divij Mathew,Zhuoyu Wen,Nancy A. Speck,Alexis Battle,Shelley L. Berger,E. John Wherry,Junwei Shi +27 more
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TLDR
In this paper, the authors developed an in-vivo T-cell CRISPR screening platform and identified a key mechanism restraining TEFF biology through the ETS family TF, Fli1.About:
This article is published in Cell.The article was published on 2021-03-04. It has received 74 citations till now.read more
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High-content CRISPR screening
TL;DR: Bock et al. as mentioned in this paper described the basic and advanced concepts of CRISPR screening and its application as a flexible and reliable method for biological discovery, biomedical research and drug development, with a special emphasis on high-content methods that make it possible to obtain detailed biological insights directly as part of the screen.
Journal ArticleDOI
High-content CRISPR screening
Christopher J Bock,Paul Datlinger,Florence M. Chardon,Matthew A. Coelho,Matthew B. Dong,Keith A. Lawson,Tian Lu,Laetitia Maroc,Thomas M. Norman,Bicna Song,Geoff Stanley,Sidi Chen,Mathew J. Garnett,Wei Li,Jason Moffat,Lei S. Qi,Rebecca S. Shapiro,Jay Shendure,Jonathan S. Weissman,Xiao-Xi Zhuang +19 more
Journal ArticleDOI
A genome-scale screen for synthetic drivers of T cell proliferation
Mateusz Legut,Zoran Gajic,Maria Francesca Guarino,Zharko Daniloski,J. Rahman,Xinhe Xue,Congyi Lu,Lu Lu,Eleni P. Mimitou,Stephanie Hao,Teresa Davoli,Catherine Diefenbach,Peter Smibert,Neville E. Sanjana +13 more
TL;DR: In this paper , the authors identify positive regulators of T cell functions through overexpression of around 12,000 barcoded human open reading frames (ORFs), which increased the proliferation and activation of primary human CD4+ and CD8+ T cells and their secretion of key cytokines such as interleukin-2 and interferonγ.
Journal ArticleDOI
Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence
TL;DR: In this paper , the authors provided an atlas of the genetic regulators of T cell exhaustion and demonstrated that modulation of epigenetic state can improve T cell responses in cancer immunotherapy, which led to improved antitumor immunity.
Journal ArticleDOI
A genome-scale screen for synthetic drivers of T cell proliferation
Mateusz Legut,Zoran Gajic,Maria Francesca Guarino,Zharko Daniloski,J. Rahman,Xinhe Xue,Congyi Lu,Lu Lu,Eleni P. Mimitou,Stephanie Hao,Teresa Davoli,Catherine Diefenbach,Peter Smibert,Neville E. Sanjana +13 more
TL;DR: In this article , the authors identify positive regulators of T cell functions through overexpression of around 12,000 barcoded human open reading frames (ORFs), which increased the proliferation and activation of primary human CD4+ and CD8+ T cells and their secretion of key cytokines such as interleukin-2 and interferonγ.
References
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Journal ArticleDOI
Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells
TL;DR: It is demonstrated that PD-1 is not required for the induction of CD8+ T cell exhaustion (TEX) in chronic LCMV infection, and the absence ofPD-1 leads to more cytotoxic, but terminally differentiated TEX, with compromised long-term durability.
Journal ArticleDOI
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells
Meromit Singer,Chao Wang,Le Cong,Nemanja D. Marjanovic,Nemanja D. Marjanovic,Monika S. Kowalczyk,Huiyuan Zhang,Jackson Nyman,Kaori Sakuishi,Sema Kurtulus,David Gennert,Junrong Xia,John Y. Kwon,James Nevin,Rebecca H. Herbst,Itai Yanai,Orit Rozenblatt-Rosen,Vijay K. Kuchroo,Aviv Regev,Aviv Regev,Aviv Regev,Ana C. Anderson +21 more
TL;DR: This work analyzed population and single-cell RNA profiles of CD8(+) tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T-cell dysfunction that can be uncoupled from T cell activation, and identifies Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction.
Journal ArticleDOI
Cancer-Specific Retargeting of BAF Complexes by a Prion-like Domain.
Gaylor Boulay,Gabriel J. Sandoval,Nicolo Riggi,Sowmya Iyer,Rémi Buisson,Beverly Naigles,Mary E. Awad,Shruthi Rengarajan,Angela Volorio,Matthew J. McBride,Matthew J. McBride,Liliane C. Broye,Lee Zou,Ivan Stamenkovic,Cigall Kadoch,Cigall Kadoch,Miguel Rivera,Miguel Rivera +17 more
TL;DR: It is demonstrated that the physical properties of prion-like domains can retarget critical chromatin regulatory complexes to establish and maintain oncogenic gene expression programs in cancer.
Journal ArticleDOI
EWS-FLI1 Utilizes Divergent Chromatin Remodeling Mechanisms to Directly Activate or Repress Enhancer Elements in Ewing Sarcoma
Nicolo Riggi,Nicolo Riggi,Birgit Knoechel,Shawn M. Gillespie,Shawn M. Gillespie,Shawn M. Gillespie,Esther Rheinbay,Esther Rheinbay,Gaylor Boulay,Gaylor Boulay,Mario L. Suvà,Mario L. Suvà,Nikki E. Rossetti,Wannaporn E. Boonseng,Ozgur Oksuz,Edward B. Cook,Aurélie Formey,Anoop P. Patel,Anoop P. Patel,Melissa Gymrek,Melissa Gymrek,Vishal Thapar,Vikram Deshpande,David T. Ting,Francis J. Hornicek,G. Petur Nielsen,Ivan Stamenkovic,Martin J. Aryee,Martin J. Aryee,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein,Miguel Rivera,Miguel Rivera +33 more
TL;DR: Divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators while activating oncogenes and potential therapeutic targets, such as the kinase VRK1.
Journal ArticleDOI
Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection.
Chen Yao,Hong-Wei Sun,Neal E. Lacey,Yun Ji,E. Ashley Moseman,E. Ashley Moseman,Han-Yu Shih,Elisabeth F. Heuston,Martha Kirby,Stacie M. Anderson,Jun Cheng,Omar Khan,Robin Handon,Julie Reilley,Jessica Fioravanti,Jinhui Hu,Selamawit Gossa,E. John Wherry,Luca Gattinoni,Dorian B. McGavern,John J. O'Shea,Pamela L. Schwartzberg,Tuoqi Wu,Tuoqi Wu +23 more
TL;DR: It is found that progenitor-like CD8+ T cells became distinct from memory precursor cells before the peak of the T cell response and the transcription factor TOX was identified as essential to endow ‘stemness’ and long-term persistence in the face of chronic infection.
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