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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.

Mutations in a person's genome can cause a number of different diseases. When mutations arise in blood stem cells and immature blood cells, blood cell development becomes misregulated and diseases such as systemic mastocytosis, myeloproliferative neoplasia, and other types of blood cancer can then occur. Through a combination of the latest techniques, so-called 'single-cell multi-omics', it is now possible to create a clear and almost complete picture of how blood cell development is incorrect in individual patients. The purpose of my research is to create maps of blood cell development for patients with systemic mastocytosis and myeloproliferative neoplasias, above all chronic myeloid leukemia, as well as healthy ones. By generating blood cell maps at diagnosis and during the course of treatment, one can examine the prognosis, see if the treatment has the desired effect and how much of the disease remains. The results of the study facilitate the diagnosis and prognostication of blood cancer, as the blood cell maps of new patients can be compared with previous cases of established blood cancer cases and healthy ones. The hope is that when enough patients are studied, the blood cell maps of newly diagnosed patients can be analyzed to tailor an optimal treatment. Since you will easily see how blood cell development is misregulated upon diagnosis, we hope in the future to be able to find new drugs that restore blood cell development to a normal state.

Mutations in genes can cause a variety of diseases. When mutations occur in blood stem cells and immature blood cells, blood cell development is misregulated and diseases such as systemic mastocytosis, myeloproliferative neoplasms, and other types of blood cancer can then occur. Diagnosis of patients today requires evaluation of a line samples with a variety of techniques. Through a new technology - so-called "single-cell RNA sequencing" - one can now analyze all genes expressed by tens of thousands of individual immature blood cells. This allows you to quickly get a clear picture of if and how the blood cell development is incorrect in a patient. The purpose of my research is to create maps of blood cell development for patients with systemic mastocytosis and myeloproliferative neoplasms and healthy. By generating blood cell maps at diagnosis and during treatment Once you can see if the treatment has the desired effect and how much of the disease is left. The results of the study facilitate the diagnosis of blood cancer, as new patients' blood cell maps can be compared with previous cases of diagnosed blood cancer cases and healthy. When enough patients are studied, we will come hopefully be able to analyze new patients' blood cell maps to tailor an optimal treatment. Since you will easily see how blood cell development is misregulated at diagnosis, so we hope in the future to be able to find new drugs that restore blood cell development to normal.

Mutations in genes can cause a variety of diseases. When mutations occur in blood stem cells and immature blood cells, blood cell development is misregulated and diseases such as systemic mastocytosis, myeloproliferative neoplasms, and other types of blood cancer can then occur. Diagnosis of patients today requires evaluation of a line samples with a variety of techniques. Through a new technology - so-called "single-cell RNA sequencing" - one can now analyze all genes expressed by tens of thousands of individual immature blood cells. This allows you to quickly get a clear picture of if and how the blood cell development is incorrect in a patient. The purpose of my research is to create maps of blood cell development for patients with systemic mastocytosis and myeloproliferative neoplasms and healthy. By generating blood cell maps at diagnosis and during treatment Once you can see if the treatment has the desired effect and how much of the disease is left. The results of the study facilitate the diagnosis of blood cancer, as new patients' blood cell maps can be compared with previous cases of diagnosed blood cancer cases and healthy. When enough patients are studied, we will come hopefully be able to analyze new patients' blood cell maps to tailor an optimal treatment. Since you will easily see how blood cell development is misregulated at diagnosis, so we hope in the future to be able to find new drugs that restore blood cell development to normal.