Cytokine Signaling Guides Blood Cell Formation

A recent paper described newly discovered insights into the processes that guide formation of various types of blood cells from their origin as hematopoietic stem cells.

Investigators at The Walter and Eliza Hall Institute (Victoria, Australia) studied the molecular signals that cause various subsets of blood progenitor cells – the progeny of hematopoietic stem cells - to expand and develop into mature blood cells. In particular, they assessed the in vitro and in vivo megakaryocyte and platelet potential of defined progenitor populations in adult mouse bone marrow.

Megakaryocytes are derived from hematopoietic stem cell precursor cells in the bone marrow. These pluripotent stem cells live in the marrow sinusoids and are capable of producing all types of blood cells depending on the signals they receive. The primary signal for megakaryocyte production is thrombopoietin (TPO). Once the cell has completed differentiation and become a mature megakaryocyte, it begins the process of producing platelets. Thrombopoietin plays a role in inducing the megakaryocyte to form small proto-platelet processes.

Details published in the January 30, 2012, online edition of the journal Proceedings of the [US] National Academy of Sciences revealed that megakaryocytes arise from CD150+ bipotential progenitors that display both platelet- and erythrocyte-producing potential in vivo and that can develop from the Flt3− fraction of the pregranulocyte-macrophage population.

Contributing author Dr. Maria Kauppi, a postdoctoral fellow at The Walter and Eliza Hall Institute, said, “We could regulate whether the progenitor cell became a megakaryocyte or a red blood cell by using different combinations of cytokines. We used a suite of cell surface markers specific to these progenitor cells that allowed us to isolate and characterize the cells. Now that we have properly identified the major cells and determined how they respond to cytokine signals involved in red blood cell and platelet production, the stage is set for understanding how these progenitors are affected in health and disease. We can also better understand, for instance, how genetic changes may lead to the development of certain blood diseases.”

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The Walter and Eliza Hall Institute