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
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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
Transcription factor IRF4 Promotes CD8 + T cell exhaustion and limits the development of memory-like T cells during chronic infection
Kevin Man,Sarah S. Gabriel,Yang Liao,Yang Liao,Renee Gloury,Renee Gloury,Simon Preston,Simon Preston,Darren C. Henstridge,Marc Pellegrini,Marc Pellegrini,Dietmar Zehn,Friederike Berberich-Siebelt,Mark A. Febbraio,Wei Shi,Wei Shi,Axel Kallies,Axel Kallies +17 more
TL;DR: A transcriptional module consisting of the TCR‐induced transcription factors IRF4, BATF, and NFATc1 that drives T cell exhaustion and impairs memory T cell development is identified.
Journal ArticleDOI
The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells
Makoto Kurachi,R. Anthony Barnitz,Nir Yosef,Pamela M. Odorizzi,Michael A. DiIorio,Madeleine E. Lemieux,Kathleen B. Yates,Jernej Godec,Martin G Klatt,Aviv Regev,E. John Wherry,W. Nicholas Haining +11 more
TL;DR: A fundamental role is identified for BATF in regulating the differentiation of effector of CD8+ T cells and this checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved.
Journal ArticleDOI
Genome-wide Analysis of Simultaneous GATA1/2, RUNX1, FLI1, and SCL Binding in Megakaryocytes Identifies Hematopoietic Regulators
Marloes R. Tijssen,Marloes R. Tijssen,Ana Cvejic,Ana Cvejic,Anagha Joshi,Rebecca Hannah,Rita Ferreira,Ariel Forrai,Dana C. Bellissimo,Dana C. Bellissimo,S. Helen Oram,Peter A. Smethurst,Nicola K. Wilson,Xiaonan Wang,Katrin Ottersbach,Derek L. Stemple,Anthony R. Green,Willem H. Ouwehand,Willem H. Ouwehand,Berthold Göttgens +19 more
TL;DR: Multifactor ChIP-Seq analysis in primary human cells coupled with a high-throughput in vivo perturbation screen offers a powerful strategy to identify essential regulators of complex mammalian differentiation processes.
Journal ArticleDOI
Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development
John E. Pimanda,Katrin Ottersbach,Kathy Knezevic,Sarah Kinston,Wan Y I Chan,Nicola K. Wilson,Josette Renée Landry,Andrew D. Wood,Anja Kolb-Kokocinski,Anthony R. Green,David Tannahill,Georges Lacaud,Valerie Kouskoff,Berthold Göttgens +13 more
TL;DR: The three HSC enhancers in these tissues and in ES cell-derived hemangioblast equivalents are bound by each of these transcription factors (TFs) and form a fully connected triad that constitutes a previously undescribed example of both this network motif in mammalian development and a GRN kernel operating during the specification of a mammalian stem cell.
Journal ArticleDOI
Progressive Loss of Memory T Cell Potential and Commitment to Exhaustion during Chronic Viral Infection
TL;DR: It is demonstrated that CD8 T cell exhaustion is a progressive developmental process, where early during chronic infection, the fate of virus-specificCD8 T cells remains plastic, while later, exhausted CD9 T cells become fixed in their differentiation state.
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