000124770 001__ 124770
000124770 005__ 20230212185124.0
000124770 0247_ $$2CORDIS$$aG:(EU-Grant)742883$$d742883
000124770 0247_ $$2CORDIS$$aG:(EU-Call)ERC-2016-ADG$$dERC-2016-ADG
000124770 0247_ $$2originalID$$acorda__h2020::742883
000124770 035__ $$aG:(EU-Grant)742883
000124770 150__ $$aEndogenous barcoding for in vivo fate mapping of lineage development in the blood and immune system$$y2017-07-01 - 2023-06-30
000124770 371__ $$aDEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG$$bGERMAN CANCER RESEARCH CENTER$$dGermany$$ehttp://www.dkfz.de$$vCORDIS
000124770 372__ $$aERC-2016-ADG$$s2017-07-01$$t2023-06-30
000124770 450__ $$aBARCODED-CELLTRACING$$wd$$y2017-07-01 - 2023-06-30
000124770 5101_ $$0I:(DE-588b)5098525-5$$2CORDIS$$aEuropean Union
000124770 680__ $$aThe 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.
000124770 909CO $$ooai:juser.fz-juelich.de:835492$$pauthority$$pauthority:GRANT
000124770 909CO $$ooai:juser.fz-juelich.de:835492
000124770 970__ $$aoai:dnet:corda__h2020::ef817164e7886a1b65fb52bb9120995c
000124770 980__ $$aG
000124770 980__ $$aCORDIS
000124770 980__ $$aAUTHORITY