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Single cell genomic analysis and perturbations of hematopoietic progenitors: Towards a refined model of hematopoiesis

Objective

Hematopoiesis is an important model for stem cell differentiation with great medical significance.
Heterogeneity within hematopoietic progenitor populations has considerably limited characterization and
molecular understanding of lineage commitment in both health and disease. Advances in single-cell genomic
technologies provide an extraordinary opportunity for unbiased and high resolution mapping of biological
function and regulation. Recently we have developed an experimental and analytical method, termed
massively parallel single-cell RNA-Seq (MARS-Seq), for unbiased classification of individual cells from
their native context and successfully applied it for characterization of immune and hematopoietic
progenitors.

Here, we propose to uncover the hierarchy and regulatory mechanisms controlling hematopoiesis by
combining comprehensive single-cell RNA-Seq analyses, modelling approaches, advanced functional assays,
single-cell CRISPR screens, knockout models and epigenetic profiling. Exciting preliminary result show that
indeed our approach is starting to uncover the complexity of hematopoietic progenitors and the regulatory
circuits driving hematopoietic decisions. We will pursue the following aims: (i) Generate a refined model of
hematopoiesis by comprehensive single-cell RNA-Seq profiling of hematopoietic progenitors, (ii) validate
the predicted model by in vivo functional developmental assays and then (iii) test candidate transcription and
chromatin factors uncovered by our model for their role in controlling progression towards various lineages
using single-cell measurements combined with CRISPR screens. Together, our study is expected to generate
a revised and high-resolution hematopoietic model and decipher the regulatory networks that control
hematopoiesis. Our methods and models may provide a platform for future medical advancements including
a large-scale European collaborative project to discover a comprehensive human hematopoietic tree.

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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-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-COG

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Host institution

WEIZMANN INSTITUTE OF SCIENCE
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.

€ 2 000 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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Activity type
Higher or Secondary Education Establishments
Links
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.

€ 2 000 000,00

Beneficiaries (1)

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