About the Project
Hematopoietic stem cells (HSCs) all share the ability to self-renew, and to reconstitute hematopoiesis in the long term. However, their production of the different hematopoietic cell types is highly variable: by transplanting single HSCs we have found that some HSCs produce all hematopoietic cell types, whereas others produce predominantly platelets, myeloid cell or lymphoid cells. To understand the physiological significance of HSC heterogeneity this project will investigate how the different HSC subtypes respond to emergency hematopoiesis. By challenging biased HSCs with the key cytokines involved in the response to anemia (Epo) and infection (GM-CSF, G-CSF), and by using physiological anemia and infection models, we will determine which HSC subsets participate in the different emergency responses, and how this allows the organism to simultaneously deal with multiple challenges. The functional studies will be complemented with single-cell level gene expression profiling to identify the molecular determinants of cytokine responsiveness within the HSC compartment.
This project will be based in the MRC Molecular Hematology Unit at the Weatherall Institute of Molecular Medicine, with access to state-of-the-art facilities. The project provides an opportunity for training in a broad range of different techniques.
In addition to training opportunities through the University, in the WIMM we run a course on basic techniques for new students of approximately 20 lectures. There are also courses on Immunology and Bioinformatics and others may be added. Institute Seminars are held on a weekly basis and regularly attract world-class scientists in haematopoiesis research. Informal exchange of ideas in the coffee area is encouraged and is an attractive feature of the WIMM.
References
GROVER A, MANCINI E, MOORE S, MEAD AJ, ATKINSON D, RASMUSSEN KD, O'CARROLL D, JACOBSEN SE, NERLOV C. 2014. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate. J. Exp. Med., 211 (2), pp. 181-8.
SANJUAN-PLA A, MACAULAY IC, JENSEN CT, WOLL PS, LUIS TC, MEAD A, MOORE S, CARELLA C, MATSUOKA S, BOURIEZ JONES T, CHOWDHURY O, STENSON L, LUTTEROPP M, GREEN JC, FACCHINI R, BOUKARABILA H, GROVER A, GAMBARDELLA A, THONGJUEA S, CARRELHA J, TARRANT P, ATKINSON D, CLARK SA, NERLOV C, JACOBSEN SE. 2013. Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature, 502 (7470), pp. 232-6.