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Endogenous barcoding for in vivo fate mapping of lineage development in the bloo...

Endogenous barcoding for in vivo fate mapping of lineage development in the blood and immune system 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 hematopoi... see more

30/06/2023

GERMAN CANCER RESE...

3M€

Project Budget: 3M€

Project leader

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

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Financing granted El organismo H2020 notifico la concesión del proyecto The day 2023-06-30

ERC-2016-ADG: ERC Advanced Grant Scope:Objectives

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Cerrada does 8 years

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Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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2 Participantes

GERMAN CANCER RESEARCH CENTE...

2.50M€ | Leader

CROMOGENIA UNITS

434.65K€ | participant

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Project duration: 73 months Date Start: 2017-05-10
End date: 2023-06-30

Project leader

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 3M€

participation deadline Sin fecha límite de participación.

Project description 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.

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