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Front Cell Dev Biol. 2019 Jun 18;7:104. doi: 10.3389/fcell.2019.00104. eCollection 2019.

Modeling the Hematopoietic Landscape.

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Institute of Clinical Sciences - Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
National University of Ireland Galway, Galway, Ireland.


Some time ago, we proposed a continuum-like view of the lineages open to hematopoietic stem cells (HSCs); each HSC self-renews or chooses from the spectrum of all end-cell options and can then "merely" differentiate. Having selected a cell lineage, an individual HSC may still "step sideways" to an alternative, albeit closely related, fate: HSC and their progeny therefore remain versatile. The hematopoietic cytokines erythropoietin, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, granulocyte/macrophage colony-stimulating factor and ligand for the fms-like tyrosine kinase 3 instruct cell lineage. Sub-populations of HSCs express each of the cytokine receptors that are positively auto-regulated upon cytokine binding. Many years ago, Waddington proposed that the epigenetic landscape played an important role in cell lineage choice. This landscape is dynamic and unstable especially regarding DNA methylation patterns across genomic DNA. This may underlie the receptor diversity of HSC and their decision-making.


blood cells; fate determination; hematopoiesis; hematopoietic stem cells; immune cells

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