Group : From haematopoietic stem cell to megakaryocyte
This group belongs to the UMR 1170 “Normal and pathological haematopoiesis”
The megakaryocyte differentiation (MK-poiesis) providing platelet production involves two almost unique biological mechanisms in a model of cell differentiation: a polyploidisation through a process called endomitosis and production of mature cells (platelets) in a dynamic mechanism of cytoplasm fragmentation of platelet precursors, megakaryocytes (MKs). Many hereditary or malignant diseases affect MK-poiesis and lead either to thrombocytopenia or to thrombocytosis. These pathologies affect either:
- signalling pathways, particularly TPO/MPL/JAK2 axis or
- transcription factors such as GATA1 and RUNX1 grouped into multiprotein complex transcriptional repressors or activators depending on the stage of differentiation,
- their effectors, and
- small GTPases.
Interestingly, the regulation of MK-poiesis is very close to that of haematopoietic stem cells including the signalling TPO/MPL pathway and the same transcription factors such as RUNX1, GATA1 and 2, TAL/SCL resulting in both defects at early stages of haematopoiesis (HSC/HP*) and during megakaryopoiesis.
The common topic of our group is focused on the study of HSC and MK-poiesis in hereditary thrombocytopenias predisposing or not to leukaemia and in hereditary and acquired myeloproliferative neoplasms (MPN) such as myelofibrosis and essential thrombocytosis. The hereditary thrombocytopenias and MPN could affect not only the definitive but also primitive haematopoiesis, thus one of our aims is also to understand the ontogeny of haematopoiesis.
*HSC: haematopoietic stem cell, HP: haematopoietic progenitor, MKs: megakaryocytes