Single-cell multi-omics analysis charts the basophil and mast cell differentiation trajectories in normal and aberrant hematopoiesis

Significant efforts have been made to map the differentiation of hematopoietic stem and progenitor cells into the various myelo-erythroid cell types.

However, the basophil and mast cell differentiation trajectories in human hematopoiesis have yet to be charted in detail.

Here, we will leverage single-cell multi-omics approaches with mutation analyses and cell fate assays to resolve a comprehensive roadmap of basophil and mast cell differentiation in health and hematologic disease.

This is complemented with high-precision validation experiments, including genetic perturbations of primary cells, to gain mechanistic insights into normal and deregulated hematopoiesis.The research described in this proposal focuses on 1) health, 2) the hematologic neoplasm systemic mastocytosis, driven by the accumulation of aberrant mast cells, and 3) chronic myeloid leukemia, in which basophilia is associated with poor prognosis.

My team of experimental and computational researchers combined with well-established clinical collaborations constitute a strong foundation to decipher basophil and mast cell differentiation in these conditions.

We hope that the described research contributes to discoveries of novel diagnostic markers and the identification of factors that drive disease development – laying the groundwork for new and improved treatment strategies.