Versatility of stem and progenitor cells and the instructive actions of cytokines on hematopoiesis

Abstract

For many years, developing hematopoietic cells have been strictly compartmentalized into a rare population of multi-potent self-renewing hematopoietic stem cells (HSC), multi-potent hematopoietic progenitor cells (MPP) that are undergoing commitment to particular lineage fates, and recognizable precursor cells that mature towards functional blood and immune cells. A single route to each end-cell type is prescribed in the “classical” model for the architecture of hematopoiesis. Recent findings have led to the viewpoint that HSCs and MPPs are more versatile than previously thought. Underlying this are multiple routes to a particular fate and cells having clandestine fate options even when they have progressed some way along a pathway. The primary role of cytokines during hematopoiesis has long been seen to be regulation of the survival and proliferation of developing hematopoietic cells. Some cytokines now clearly have instructive actions on cell-fate decisions. All this leads to a new way of viewing hematopoiesis whereby versatile HSC and MPP are directed towards lineage outcomes via cytokine regulated cell-fate decisions. This means greater flexibility to the shaping of hematopoiesis.

• Cell differentiation
• cell-fate decisions
• cytokines
• hematopoiesis
• leukemia

Declaration of interest

The authors alone are responsible for the content and writing of the paper.

The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013 under Research Executive Agency grant agreement № 315902. C.J.M., L.A.S. and L.vM. gratefully acknowledge receipt of a Marie Curie Research Associate post. G.B., K.T., R.C. and A.R. are partners within the Marie Curie Initial Training Network DECIDE (Decision-making within cells and differentiation entity therapies).