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Modeling the Hematopoietic Landscape.

Geoffrey Brown1, Rhodri Ceredig2

  • 1Institute of Clinical Sciences - Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

Frontiers in Cell and Developmental Biology
|July 6, 2019
PubMed
Summary
This summary is machine-generated.

Hematopoietic stem cells (HSCs) possess versatile lineage choices, capable of self-renewal or differentiation. Cytokine signaling and dynamic epigenetic landscapes, including DNA methylation, influence HSC fate decisions and receptor diversity.

Keywords:
blood cellsfate determinationhematopoiesishematopoietic stem cellsimmune cells

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Area of Science:

  • Hematology
  • Stem Cell Biology
  • Epigenetics

Background:

  • Hematopoietic stem cells (HSCs) exhibit plasticity, allowing self-renewal or differentiation into various cell types.
  • HSCs can switch to closely related lineages, maintaining versatility throughout their progeny.
  • Cytokines like erythropoietin and G-CSF are key regulators of hematopoietic cell lineage specification.

Purpose of the Study:

  • To explore the continuum of lineage choices available to hematopoietic stem cells (HSCs).
  • To investigate the role of cytokine signaling in instructing HSC lineage decisions.
  • To examine the influence of epigenetic factors, specifically DNA methylation, on HSC fate determination.

Main Methods:

  • Analysis of HSC self-renewal and differentiation pathways.
  • Investigating the expression and auto-regulation of cytokine receptors on HSC subpopulations.
  • Examining dynamic changes in DNA methylation patterns within the epigenetic landscape.

Main Results:

  • HSCs operate on a continuum of lineage options, allowing for both self-renewal and differentiation.
  • Specific hematopoietic cytokines bind to corresponding receptors on HSCs, directing lineage commitment.
  • Dynamic epigenetic landscapes, particularly DNA methylation, are implicated in HSC receptor diversity and decision-making.

Conclusions:

  • HSC lineage plasticity is maintained through a spectrum of choices and potential lineage 'sideways steps'.
  • Cytokine receptor expression and auto-regulation are critical for instructing cell fate.
  • The dynamic nature of the epigenetic landscape, especially DNA methylation, likely underlies HSC versatility and lineage selection.