HemTree2.0 (724471)

  https://cordis.europa.eu/project/id/724471

  Horizon 2020 (2014-2020)

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

  ERC Consolidator Grant (ERC-2016-COG)

  genetics  ·  stem cells

  2017-10-01 Start Date (YY-MM-DD)

  2022-09-30 End Date (YY-MM-DD)

  € 2,000,000 Total Cost

  Description

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.

  Complicit Organisations

1 Israeli organisation participates in HemTree2.0.