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Haematopoiesis

Refining mixed-lineage progenitors

Nature Reviews Immunology volume 6, pages 710–711 (2006)Cite this article

A common feature of cell-fate specification in haematopoiesis is the existence of multipotent progenitors with low levels of multilineage gene expression. This indicates that commitment to a particular lineage requires both the induction and the repression of sets of lineage-specific genes. Harinder Singh and colleagues have examined the regulatory mechanisms that are responsible for this process during the commitment of common myeloid progenitors (CMPs) to the macrophage or neutrophil lineage.

Using genome-wide expression analysis, EGR2 (early growth response 2) and NAB2 (NGFI-A (EGR1)-binding protein 2) were identified as being induced by high levels of PU.1 in CMPs. Induction of PU.1 activity in PUERhi cells in which the expression of EGR2 had been blocked led to a mixed macrophage and neutrophil morphology and a mixed pattern of gene expression. Eighteen neutrophil-specific genes that are repressed by EGR2 and NAB2 functioning together were identified. So it seems that low levels of PU.1 initially activate a mixed-lineage pattern, but as the amount of PU.1 increases, PU.1 induces the expression of EGR2 and NAB2, resulting in entry to the macrophage differentiation pathway and repression of neutrophil differentiation.

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ORIGINAL RESEARCH PAPER

  1. Lasio, P. et al. Multilineage transcriptional priming and determination of alternate hematopoietic cell fates. Cell 126, 755–766 (2006)

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  1. Kirsty Minton
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Minton, K. Refining mixed-lineage progenitors. Nat Rev Immunol 6, 710–711 (2006). https://doi.org/10.1038/nri1947

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  • DOI: https://doi.org/10.1038/nri1947

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