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HemTree2.0 SIGNED

Single cell genomic analysis and perturbations of hematopoietic progenitors: Towards a refined model of hematopoiesis

Total Cost €

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EC-Contrib. €

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Partnership

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 HemTree2.0 project word cloud

Explore the words cloud of the HemTree2.0 project. It provides you a very rough idea of what is the project "HemTree2.0" about.

epigenetic    disease    candidate    networks    commitment    progression    uncovered    individual    massively    starting    analytical    discover    screens    advancements    populations    pursue    differentiation    complexity    heterogeneity    combined    models    cell    progenitor    mapping    rna    single    preliminary    resolution    limited    termed    progenitors    uncover    human    opportunity    technologies    medical    profiling    molecular    crispr    decipher    assays    function    transcription    tree    native    circuits    hematopoiesis    considerably    model    context    validate    revised    decisions    successfully    vivo    biological    chromatin    lineage    immune    combining    extraordinary    unbiased    hierarchy    collaborative    regulation    generate    seq    predicted    mechanisms    regulatory    genomic    hematopoietic    parallel    stem    lineages    significance    platform    mars    driving    functional    experimental    developmental    knockout    classification    characterization    refined    cells    health   

Project "HemTree2.0" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Israel [IL]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2022-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 2˙000˙000.00

Map

 Project objective

Hematopoiesis is an important model for stem cell differentiation with great medical significance. Heterogeneity within hematopoietic progenitor populations has considerably limited characterization and molecular understanding of lineage commitment in both health and disease. Advances in single-cell genomic technologies provide an extraordinary opportunity for unbiased and high resolution mapping of biological function and regulation. Recently we have developed an experimental and analytical method, termed massively parallel single-cell RNA-Seq (MARS-Seq), for unbiased classification of individual cells from their native context and successfully applied it for characterization of immune and hematopoietic progenitors.

Here, we propose to uncover the hierarchy and regulatory mechanisms controlling hematopoiesis by combining comprehensive single-cell RNA-Seq analyses, modelling approaches, advanced functional assays, single-cell CRISPR screens, knockout models and epigenetic profiling. Exciting preliminary result show that indeed our approach is starting to uncover the complexity of hematopoietic progenitors and the regulatory circuits driving hematopoietic decisions. We will pursue the following aims: (i) Generate a refined model of hematopoiesis by comprehensive single-cell RNA-Seq profiling of hematopoietic progenitors, (ii) validate the predicted model by in vivo functional developmental assays and then (iii) test candidate transcription and chromatin factors uncovered by our model for their role in controlling progression towards various lineages using single-cell measurements combined with CRISPR screens. Together, our study is expected to generate a revised and high-resolution hematopoietic model and decipher the regulatory networks that control hematopoiesis. Our methods and models may provide a platform for future medical advancements including a large-scale European collaborative project to discover a comprehensive human hematopoietic tree.

 Publications

year authors and title journal last update
List of publications.
2018 Amir Giladi, Ido Amit
Single-Cell Genomics: A Stepping Stone for Future Immunology Discoveries
published pages: 14-21, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.11.011
Cell 172/1-2 2019-06-06
2018 Guy Ledergor, Assaf Weiner, Mor Zada, Shuang-Yin Wang, Yael C. Cohen, Moshe E. Gatt, Nimrod Snir, Hila Magen, Maya Koren-Michowitz, Katrin Herzog-Tzarfati, Hadas Keren-Shaul, Chamutal Bornstein, Ron Rotkopf, Ido Yofe, Eyal David, Venkata Yellapantula, Sigalit Kay, Moshe Salai, Dina Ben Yehuda, Arnon Nagler, Lev Shvidel, Avi Orr-Urtreger, Keren Bahar Halpern, Shalev Itzkovitz, Ola Landgren, Jesus San-Miguel, Bruno Paiva, Jonathan J. Keats, Elli Papaemmanuil, Irit Avivi, Gabriel I. Barbash, Amos Tanay, Ido Amit
Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma
published pages: 1867-1876, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0269-2
Nature Medicine 24/12 2019-06-06
2017 Hadas Keren-Shaul, Amit Spinrad, Assaf Weiner, Orit Matcovitch-Natan, Raz Dvir-Szternfeld, Tyler K. Ulland, Eyal David, Kuti Baruch, David Lara-Astaiso, Beata Toth, Shalev Itzkovitz, Marco Colonna, Michal Schwartz, Ido Amit
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
published pages: 1276-1290.e17, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.05.018
Cell 169/7 2019-06-06
2018 Amir Giladi, Franziska Paul, Yoni Herzog, Yaniv Lubling, Assaf Weiner, Ido Yofe, Diego Jaitin, Nina Cabezas-Wallscheid, Regine Dress, Florent Ginhoux, Andreas Trumpp, Amos Tanay, Ido Amit
Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis
published pages: 836-846, ISSN: 1465-7392, DOI: 10.1038/s41556-018-0121-4
Nature Cell Biology 20/7 2019-06-06
2019 Ronnie Blecher-Gonen, Pierre Bost, Kerry L. Hilligan, Eyal David, Tomer Meir Salame, Elsa Roussel, Lisa M. Connor, Johannes U. Mayer, Keren Bahar Halpern, Beáta Tóth, Shalev Itzkovitz, Benno Schwikowski, Franca Ronchese, Ido Amit
Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity
published pages: 109-121.e6, ISSN: 2405-4712, DOI: 10.1016/j.cels.2019.01.001
Cell Systems 8/2 2019-06-06
2016 Diego Adhemar Jaitin, Assaf Weiner, Ido Yofe, David Lara-Astiaso, Hadas Keren-Shaul, Eyal David, Tomer Meir Salame, Amos Tanay, Alexander van Oudenaarden, Ido Amit
Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq
published pages: 1883-1896.e15, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.11.039
Cell 167/7 2019-06-06
2019 Hanjie Li, Anne M. van der Leun, Ido Yofe, Yaniv Lubling, Dikla Gelbard-Solodkin, Alexander C.J. van Akkooi, Marlous van den Braber, Elisa A. Rozeman, John B.A.G. Haanen, Christian U. Blank, Hugo M. Horlings, Eyal David, Yael Baran, Akhiad Bercovich, Aviezer Lifshitz, Ton N. Schumacher, Amos Tanay, Ido Amit
Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma
published pages: 775-789.e18, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.11.043
Cell 176/4 2019-06-06
2018 Merav Cohen, Amir Giladi, Anna-Dorothea Gorki, Dikla Gelbard Solodkin, Mor Zada, Anastasiya Hladik, Andras Miklosi, Tomer-Meir Salame, Keren Bahar Halpern, Eyal David, Shalev Itzkovitz, Tibor Harkany, Sylvia Knapp, Ido Amit
Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting
published pages: 1031-1044.e18, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.09.009
Cell 175/4 2019-06-06
2018 Chamutal Bornstein, Shir Nevo, Amir Giladi, Noam Kadouri, Marie Pouzolles, François Gerbe, Eyal David, Alice Machado, Anna Chuprin, Beáta Tóth, Ori Goldberg, Shalev Itzkovitz, Naomi Taylor, Philippe Jay, Valérie S. Zimmermann, Jakub Abramson, Ido Amit
Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells
published pages: 622-626, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0346-1
Nature 559/7715 2019-06-06
2017 Chiara Medaglia, Amir Giladi, Liat Stoler-Barak, Marco De Giovanni, Tomer Meir Salame, Adi Biram, Eyal David, Hanjie Li, Matteo Iannacone, Ziv Shulman, Ido Amit
Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq
published pages: 1622-1626, ISSN: 0036-8075, DOI: 10.1126/science.aao4277
Science 358/6370 2019-06-06

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