Haemogenic endocardium contributes to transient definitive haematopoiesis

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 Pashmforoush, Hanna K. A. Mikkola and Atsushi Nakano ()
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Haruko Nakano: University of California, Los Angeles
Xiaoqian Liu: University of California, Los Angeles
Armin Arshi: University of California, Los Angeles
Yasuhiro Nakashima: University of California, Los Angeles
Ben van Handel: University of California, Los Angeles
Rajkumar Sasidharan: University of California, Los Angeles
Andrew W. Harmon: University of California, Los Angeles
Jae-Ho Shin: University of California, Los Angeles
Robert J. Schwartz: University of Houston
Simon J. Conway: Medical and Molecular Genetics, Biochemistry and Molecular Biology, Indiana University School of Medicine
Richard P. Harvey: the Victor Chang Cardiac Research Institute
Mohammad Pashmforoush: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California Keck School of Medicine
Hanna K. A. Mikkola: University of California, Los Angeles
Atsushi Nakano: University of California, Los Angeles

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms2569

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