Modeling the Hematopoietic Landscape

Research output: Contribution to journalReview article

Authors

Colleges, School and Institutes

External organisations

  • National University of Ireland Galway

Abstract

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.

Details

Original languageEnglish
Article number104
Number of pages13
JournalFrontiers in cell and developmental biology
Volume7
Publication statusPublished - 18 Jun 2019

Keywords

  • hematopoiesis, hematopoietic stem cells, fate determination, blood cells, immune cells