Regulation of haematopoiesis in health and disease
Hematopoietic stem cells (HSCs) give rise to all types of blood and immune cells. Throughout the life of an organism, the majority of HSCs are quiescent. A few HSCs, however, divide frequently to produces haematopoietic cells through a specific sequence: an HSC gives rise to a progenitor cell, which then matures into a multipotent progenitor and later into a restricted progenitor. Tight regulation of the rate of stem cell division and differentiation of the progenitor cells is important for the maintenance of the healthy blood and immune cell system. Accumulation of somatic mutations and genome defects in hematopoietic stem cells and progenitor cells is a common cause for adult cancers such as acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). How mutations accumulate and lead to cancers is however poorly understood. Defining the key predispositions and underlying mechanisms will enable a better prognosis of cancer and help a patient with individual therapies.
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SELECTED PUBLICATIONS
Ramasz B, Krüger A, Reinhardt J, Sinha A, Gerlach M, Gerbaulet A, Reinhardt S, Dahl A, Chavakis T, Wielockx B, Grinenko T.Hematopoietic stem cell response to acute thrombocytopenia requires signaling through distinct receptor tyrosine kinases. Blood. 2019 Aug 21. doi: 10.1182/blood.2019000721.
Grinenko T, Eugster A, Thielecke L, Ramasz B, Krüger A, Dietz S, Glauche I, Gerbaulet A, von Bonin M, Basak O, Clevers H, Chavakis T, Wielockx B. Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice. Nat Commun.,15;9(1):1898, 2018.
Singh RP*, Grinenko T*, Ramasz B, Franke K, Lesche M, Dahl A, Gassmann M, Chavakis T, Henry I, Wielockx B. Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis during Chronic Erythroid Stress in EPO Transgenic Mice. Stem Cell Reports. 10(6):1908-1919, 2018 (*equally contributed as first authors).
Mitroulis, I., K. Ruppova, B. Wang, L.-S. Chen, M. Grzybek, Grinenko T., A. Eugster, M. Troullinaki, A. Palladini, I. Kourtzelis, A. Chatzigeorgiou, A. Schlitzer, M. Beyer, L.A.B. Joosten, B. Isermann, M. Lesche, A. Petzold, K. Simons, I. Henry, A. Dahl, J.L. Schultze, Wielockx, B., N. Zamboni, P. Mirtschink, Ü. Coskun, G. Hajishengallis, M.H. Netea, and T. Chavakis. Modulation of haematopoietic progenitors is an integral component of trained immunity. Cell, 72(1-2):147-161, 2018.
Grinenko T, Arndt K, Portz M, Mende N, Günther M, Cosgun KN, Alexopoulou D, Lakshmanaperumal N, Henry I, Dahl A, Waskow C. Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells. J Exp Med., 211 (2):209-15, 2014.
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© Marc Eisele
Grinenko Lab