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Microsatellite Barcoding: reconstructing the family tree of hematopoietic cells

Objective

While murine hematopoiesis has been considered as resolved science, recent results using barcoding, which allows the tracing of single cells in vivo, clearly show that the topology of the murine hematopoietic tree needs revisions. In parallel, human hematopoiesis has been overlooked and is widely considered as following the same tree as in mice. To leverage our understanding of normal human hematopoiesis, tools for barcoding in humans are urgently needed. This research program seeks to meet this need by taking advantage of recent developments in next generation sequencing to provide an improved barcoding method for in vivo use in human. Our microsatellite barcoding method exploits the fact that microsatellites in various loci undergo length changes during cell division, to create a natural barcode for each cell, and reconstruct the overall differentiation tree using a phylogenetic algorithm. Our technique, which is highly detailed with respect to current versions of microsatellite barcoding, provides high dimensional characterization of the cells and will allow the inference of important properties such as new phenotypic markers and key molecular regulators. Therefore, we will provide insights into both cell lineage and the molecular mechanisms involved in differentiation. With this method, we will provide the first in vivo description of the human hematopoietic tree and identify new progenitors and key molecular factors involved in human hematopoiesis. This knowledge will allow us to test whether cells with different origins have different functions, a key question in immunology in particular during infection and inflammation, and it will help design ways of therapeutically manipulating the hematopoietic system. More generally it will impact our understanding of stem cell differentiation for which hematopoiesis is used as an exemplar.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2017-STG

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Host institution

INSTITUT CURIE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 154 375,00
Address
RUE D ULM 26
75231 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 500 000,00

Beneficiaries (2)

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