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 Blood, 15 December 2008, Vol. 112, No. 13, pp. 4895-4904.
Prepublished online as a Blood First Edition Paper on September 19, 2008; DOI 10.1182/blood-2007-12-123836.

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Submitted December 6, 2007
Accepted June 23, 2008

Interleukin-1 mediated hematopoietic cell regulation in the aorta-gonad-mesonephros region of the mouse embryo

Claudia Orelio, Esther Haak, Marian Peeters, and Elaine Dzierzak*

Cell Biology, Erasmus University MC, Rotterdam, Netherlands

* Corresponding author; email: e.dzierzak{at}erasmusmc.nl.

Hematopoiesis during development is a dynamic process, with many factors involved in the emergence and regulation of hematopoietic stem and progenitor cells. While previous studies have focused on developmental signaling and transcription factors in embryonic hematopoiesis, the role of well-known adult hematopoietic cytokines in the embryonic hematopoietic system has been largely unexplored. The cytokine Interleukin-1 (IL-1), best known for its pro-inflammatory properties, has radio-protective effects on adult bone marrow hematopoietic stem cells (HSCs), induces HSC mobilization and increases HSC proliferation and/or differentiation. Here we examine IL-1 and its possible role in regulating hematopoiesis in the midgestation mouse embryo. We show that IL-1, IL-1 receptors and signaling mediators are expressed in the aorta-gonad-mesonephros (AGM) region during the time when HSCs emerge in this site. IL-1 signaling is functional in the AGM, and the IL-1RI is expressed ventrally in the aortic subregion by some hematopoietic, endothelial and mesenchymal cells. In vivo analyses of IL-1RI deficient embryos show an increased myeloid differentiation, concomitant with a slight decrease in AGM HSC activity. Our results suggest that IL-1 is an important homeostatic regulator at the earliest time of HSC development, acting to limit the differentiation of some HSCs along the myeloid lineage.


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C. Orelio, M. Peeters, E. Haak, K. van der Horn, and E. Dzierzak
Interleukin-1 regulates hematopoietic progenitor and stem cells in the midgestation mouse fetal liver
Haematologica, April 1, 2009; 94(4): 462 - 469.
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