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IC-CCD-qHSC SIGNED

Intrapopulation communication and collective cell decisions of hematopoietic stem cells

Total Cost €

0

EC-Contrib. €

0

Partnership

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 IC-CCD-qHSC project word cloud

Explore the words cloud of the IC-CCD-qHSC project. It provides you a very rough idea of what is the project "IC-CCD-qHSC" about.

tools    found    profiling    perceive    unknown    expand    heterogeneous    image    hematopoietic    broad    spatial    collective    preliminary    single    organization    deep    3d    forms    customized    regulation    proximal    regulated    cellular    bone    maintenance    anatomical    self    quorum    renewing    synchronously    convert    tend    hsc    hscs    cells    molecular    cell    function    embryonic    learning    neighborhoods    majority    differentiation    few    microscopy    suffices    proliferation    marrow    mechanisms    date    moment    dependencies    sensing    individual    metabolomic    proliferative    coordinated    transcriptomics    adult    rates    compensate    statistics    substantially    exit    basic    death    triggers    behavior    tissue    despite    cluster    life    preserve    homeostasis    local    homeostatic    bm    contributes    adulthood    entry    rare    combines    relatively    competition    pool    showing    quiescent    stages    stem    postnatal    blood    active    densities    tightly    interplay    frequencies    unravel    pipeline    accumulate    continuous    cycle    heterogeneity    postulate    functional    orchestrate    regions    vast    multidisciplinary    crosstalk    basal   

Project "IC-CCD-qHSC" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT ZURICH 

Organization address
address: RAMISTRASSE 71
city: ZURICH
postcode: 8006
website: n.a.

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 Switzerland [CH]
 Total cost 2˙312˙500 €
 EC max contribution 2˙312˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-COG
 Funding Scheme ERC-COG
 Starting year 2020
 Duration (year-month-day) from 2020-07-01   to  2025-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT ZURICH CH (ZURICH) coordinator 2˙312˙500.00

Map

 Project objective

Hematopoietic stem cells (HSCs) contribute to blood cell production throughout life and are found at rare, yet tightly regulated frequencies in adult bone marrow (BM). During embryonic and postnatal development, HSCs expand through continuous self-renewing proliferation. Upon entry into adulthood the vast majority of HSCs synchronously convert to a quiescent state. From then on, at any given moment very few HSCs are found in active stages of cell cycle, which suffices to compensate basal HSC loss due to differentiation or cell death. Since proliferation rates of individual HSCs are heterogeneous, entry and exit from cell cycle need to be coordinated at the level of the HSC pool. To date, the mechanisms that orchestrate this collective proliferative behavior and effectively control the maintenance of homeostatic HSC numbers remain unknown. In preliminary work for this project we have customized a pipeline that combines 3D microscopy, deep learning-based image analysis and spatial statistics. Using these tools, we observed that despite showing broad spatial heterogeneity, HSCs tend to cluster and accumulate in relatively large regions of the BM. We now postulate that molecular crosstalk between proximal HSCs enables them to perceive their local densities and triggers collective regulation of HSC function to preserve homeostasis. Through a multidisciplinary approach involving high-level microscopy, spatial analyses, comprehensive metabolomic profiling and single-cell transcriptomics we aim to 1) characterize the basic anatomical and functional features of spatial dependencies between HSCs 2) study the potential role of quorum-sensing mechanisms in HSC crosstalk and 3) investigate if competition for molecular resources in local neighborhoods contributes to maintenance of HSC homeostasis. Our research has the potential to unravel novel complex forms of cellular interplay and substantially advance our understanding of hematopoietic tissue organization.

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