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BARCODED-CELLTRACING SIGNED

Endogenous barcoding for in vivo fate mapping of lineage development in the blood and immune system

Total Cost €

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EC-Contrib. €

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Partnership

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 BARCODED-CELLTRACING project word cloud

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

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Project "BARCODED-CELLTRACING" data sheet

The following table provides information about the project.

Coordinator
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG 

Organization address
address: IM NEUENHEIMER FELD 280
city: HEIDELBERG
postcode: 69120
website: www.dkfz.de

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 Germany [DE]
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-07-01   to  2022-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG DE (HEIDELBERG) coordinator 2˙500˙000.00

Map

 Project objective

The immune system is a complex ensemble of diverse lineages. Studies on in-vivo-hematopoiesis have until now largely rested on transplantation. More physiological experiments have been limited by the inability to analyze hematopoietic stem (HSC) and progenitor cells in situ without cell isolation and other disruptive manipulations. We have developed mouse mutants in which a fluorescent marker can be switched on in HSC in situ (inducible fate mapping), and traced HSC lineage output under unperturbed conditions in vivo. These experiments uncovered marked differences comparing in situ and post-transplantation hematopoiesis. These new developments raise several important questions, notably on the developmental fates HSC realize in vivo (as opposed to their experimental potential), and on the structure (routes and nodes) of hematopoiesis from HSC to peripheral blood and immune lineages. Answers to these questions (and in fact the deconvolution of any tissue) require the development of non-invasive, high resolution barcoding systems. We have now designed, built and tested a DNA-based barcoding system, termed Polylox, that is based on an artificial recombination locus in which Cre recombinase can generate several hundred thousand genetic tags in mice. We chose the Cre-loxP system to link high resolution barcoding (i.e. the ability to barcode single cells and to fate map their progeny) to the zoo of tissue- or stage-specific, inducible Cre-driver mice. Here, I will present the principles of this endogenous barcoding system, demonstrate its experimental and analytical feasibilities and its power to resolve complex lineages. The work program addresses in a comprehensive manner major open questions on the structure of the hematopoietic system that builds and maintains the immune system. This project ultimately aims at an in depth dissection of unique or common lineage pathways emerging from HSC, and at resolving relationships within cell lineages of the immune system.

 Publications

year authors and title journal last update
List of publications.
2017 Weike Pei, Thorsten B. Feyerabend, Jens Rössler, Xi Wang, Daniel Postrach, Katrin Busch, Immanuel Rode, Kay Klapproth, Nikolaus Dietlein, Claudia Quedenau, Wei Chen, Sascha Sauer, Stephan Wolf, Thomas Höfer, Hans-Reimer Rodewald
Polylox barcoding reveals haematopoietic stem cell fates realized in vivo
published pages: 456-460, ISSN: 0028-0836, DOI: 10.1038/nature23653
Nature 548/7668 2019-04-18
2018 Thomas Höfer, Hans-Reimer Rodewald
Differentiation-based model of hematopoietic stem cell functions and lineage pathways
published pages: 1106-1113, ISSN: 0006-4971, DOI: 10.1182/blood-2018-03-791517
Blood 132/11 2019-02-12

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