Haemogenic endocardium contributes to transient definitive haematopoiesis

• DOI: 10.1038/ncomms2569
• Publication Date: 2013-03-05T09:45:32Z
• Authors: Haruko Nakano; Xiaoqian Liu; Armin Arshi; Yasuhiro Nakashima; Ben van Handel; Rajkumar Sasidharan; Andrew W. Harmon; Jae-Ho Shin; Robert J. Schwartz; Simon J. Conway; Richard P. Harvey; Mohammad Pashmfor...; Hanna K. A. Mikkola; Atsushi Nakano
• Keywords: Platelet Membrane Glycoprotein IIb; 570; 1.1 Normal biological development and functioning; Hematopoietic System; LIM-Homeodomain Proteins; Stem Cell Research - Embryonic - Non-Human; Fluorescent Antibody Technique; Cardiovascular; Article; Mice; 03 medical and health sciences; Erythroid Cells; Underpinning research; 1 Underpinning research; Animals; Myeloid Cells; Heart Atria; Homeodomain Proteins; 0303 health sciences; Endothelial Cells; Stem Cell Research; Hematopoiesis; Platelet Endothelial Cell Adhesion Molecule-1; Heart Disease; Liver; Homeobox Protein Nkx-2.5; Stem Cell Research - Nonembryonic - Non-Human; Endocardium; Transcription Factors

Haematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial and haematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a haemogenic organ akin to the dorsal aorta. Here we examine the haemogenic activity of the developing endocardium. Mouse heart explants generate myeloid and erythroid colonies in the absence of circulation. Haemogenic activity arises from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and is transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, are expressed in and required for the haemogenic population of the endocardium. Together, these data suggest that a subset of endocardial/endothelial cells serve as a de novo source for transient definitive haematopoietic progenitors.