Aorta-gonad-mesonephros

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The aorta-gonad-mesonephros (AGM)^{[1][2][3][4][5]} is a region of embryonic mesoderm that develops during embryonic development from the para-aortic splanchnopleura in chick,^[6] mouse^[4][5] and human^[7] embryos. The very first adult definitive haematopoietic stem cells, capable of long-term multilineage repopulation of adult irradiated recipients, originate from the ventral endothelial wall of the embryonic dorsal aorta,^[8][9] through an endothelial transdifferentiation process referred to as an 'endothelial-to-haematopoietic transition' (EHT).^{[10][11][12][13][14]} In the mouse embryo, these very first HSCs are characterised by their expression of Ly6A-GFP^[8][15] (Sca1), CD31,^[16][15] CD34,^[17] cKit,^[16][17] CD27,^[16] CD41,^[18] Gata2,^[16][19][13] Runx1,^[20][21] Notch1,^[22] and BMP^[23] amongst others.

The aorta-gonad-mesonephros (AGM) region is an area derived from splanchnopleura mesoderm identified in embryonic humans, mice, and non-mammalian vertebrates such as birds and zebrafish. It contains the dorsal aorta, genital ridges and mesonephros and lies between the notochord and the somatic mesoderm, extending from the umbilicus to the anterior limb bud of the embryo.^[24] The AGM region plays an important role in embryonic development, being the first autonomous intra-embryonic site for definitive haematopoiesis.^{[3][2][5][25][26]} Definitive haematopoiesis produces haematopoietic stem cells that have the capacity to 'self-renew' when serially transplanted into irradiated recipients, and differentiate into any of the blood cell lineages of the adult haematopoietic hierarchy.^[5][25] Specialised endothelial cells in the floor of the dorsal aorta (within the AGM region), identified as haemogenic endothelium, differentiate into haematopoietic stem cells.