Hematopoietic stem and progenitor cell fate decisions during acute and chronic thrombocytopenia

• Applicant: Dr. Tatyana Grinenko
• Subject Area: Hematology, Oncology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 288400467

Hematopoietic stem cells (HSCs) are unique in their capacity to self-renew and replenish the entire blood system, even after single cell transplantation into lethally irradiated recipients. They give rise to a series of multipotent progenitors (MPPs) with decreasing self-renewal potential, followed by differentiation towards committing progenitors and mature cells. Hematopoietic cell differentiation is commonly depicted as a sequential commitment process through multiple intermediate states, but the molecular mechanisms of these fate decisions is poorly understood and can differ during stress situations. Preliminary results obtained in the research group strongly suggest that HSCs and MPPs react differently upon acute thrombocytopenia with regard to their proliferation and differentiation potential. With the help of a newly available mouse line devoid of HSCs, and well established methods in our lab, I plan to identify and characterise these different pathways and the regulation of it during acute and chronic thrombocytopenia. This will not only be important to understand how the HSC compartment copes and overcomes haematological stress, but will most certainly also help to develop new strategies for immune-mediated thrombocytopenic purpura (ITP) patients.

• DFG Programme: Research Grants