title: Haemogenic endocardium contributes to transient definitive haematopoiesis.
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.
authors: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
authors: Haruko
authors: H
authors: Nakano
authors: Xiaoqian
authors: X
authors: Liu
authors: Armin
authors: A
authors: Arshi
authors: Yasuhiro
authors: Y
authors: Nakashima
authors: Ben
authors: B
authors: van Handel
authors: Rajkumar
authors: R
authors: Sasidharan
authors: Andrew W
authors: AW
authors: Harmon
authors: Jae-Ho
authors: JH
authors: Shin
authors: Robert J
authors: RJ
authors: Schwartz
authors: Simon J
authors: SJ
authors: Conway
authors: Richard P
authors: RP
authors: Harvey
authors: Mohammad
authors: M
authors: Pashmforoush
authors: Hanna K A
authors: HK
authors: Mikkola
authors: Atsushi
authors: A
authors: Nakano
mesh_terms: D000818:Animals; D004699:Endocardium / Q000166:cytology / Q000196:embryology / Q000502:physiology* / Q000648:ultrastructure; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D041905:Erythroid Cells / Q000166:cytology; D005455:Fluorescent Antibody Technique; D006325:Heart Atria / Q000166:cytology / Q000648:ultrastructure; D006410:Hematopoiesis / Q000502:physiology*; D006413:Hematopoietic System / Q000166:cytology / Q000502:physiology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040201:Platelet Membrane Glycoprotein IIb; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1