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ReproXimera SIGNED

Modelling in vivo lineage reprogramming of human astrocytes into induced neurons in the adult mouse brain

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 ReproXimera project word cloud

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

adult    context    strategies    murine    programs    transplantable    mouse    reprogramming    hipsc    hallmarks    developmental    capacity    integration    advantage    humanized    model    insights    integrate    astroglia    that    vivo    maintaining    direct    host    identity    genetic    glial    me    differentiated    ing    human    directed    implications    last    constraints    progenitors    combine    vitro    plastic    largely    sparse    fundamental    decade    reprogrammed    differ    question    takes    translation    mature    unclear    fate    counterparts    neurons    stem    cells    experimental    successful    induce    obtain    derive    editing    astroglial    markedly    pluripotent    crispr    determines    repair    pioneered    laboratory    glia    studies    plasticity    cell    tissue    astrocytes    functional    complexity    conversion    cas9    maturation    shown    undergo    underlying    brain    data    lineage    differentiation    stages    genome    grafting    conversions   

Project "ReproXimera" data sheet

The following table provides information about the project.

Coordinator
KING'S COLLEGE LONDON 

Organization address
address: STRAND
city: LONDON
postcode: WC2R 2LS
website: www.kcl.ac.uk

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 United Kingdom [UK]
 Total cost 224˙933 €
 EC max contribution 224˙933 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2020
 Duration (year-month-day) from 2020-02-01   to  2022-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KING'S COLLEGE LONDON UK (LONDON) coordinator 224˙933.00

Map

 Project objective

Studies during last decade have shown that the genetic programs underlying cell identity are plastic even in fully differentiated cells. Direct lineage reprogramming takes advantage of this plasticity to induce cell fate conversions from one cell type into another. The host laboratory is among those who have pioneered successful lineage reprogramming of glial cells into induced functional neurons in vitro and in vivo. These studies have largely focused on murine glia. While there is sparse evidence that also human glia can be reprogrammed into induced neurons, it is unclear whether such lineage conversion can occur within the constraints of the in vivo tissue context by fully integrated mature human glia. In this project I propose an experimental model to study direct lineage reprogramming of human astrocytes into induced neurons at distinct developmental stages within the context of the adult mouse brain in vivo. This model is based on previous findings that show that human astroglial progenitors can integrate into the mouse brain following grafting, maintaining hallmarks that are specific to human astroglia which differ markedly in their complexity from their murine counterparts. Here I will combine this model system with the directed glial differentiation of induced human pluripotent stem cells (hiPSC) and state-of-the-art genome-editing via CRISPR-Cas9 technology. This will enable me to derive transplantable glial progenitors that can be induced to undergo lineage conversion in a humanized in vivo context at distinct maturation stages. With this approach I will obtain important insights into the fundamental question of how the state of maturation and functional integration determines the capacity of human astroglia to undergo lineage conversion into functional neurons in vivo. I expect that the data resulting from this approach will have important implications towards the translation of direct lineage reprogramming into new strategies for brain repair.

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