title: SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development.
abstract: The study of human cardiogenesis would benefit from a detailed cell lineage fate map akin to that established for the haematopoietic lineages. Here we sought to define cell lineage relationships based on the expression of NKX2-5 and the cell surface markers VCAM1, SIRPA and CD34 during human cardiovascular development. Expression of NKX2-5(GFP) was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5(GFP/w) human embryonic stem cells (hESCs). Cardiovascular cell lineages sub-fractionated on the basis of SIRPA, VCAM1 and CD34 expression were assayed for differentiation potential and gene expression. The NKX2-5(pos)CD34(pos) population gave rise to endothelial cells that rapidly lost NKX2-5 expression in culture. Conversely, NKX2-5 expression was maintained in myocardial committed cells, which progressed from being NKX2-5(pos)SIRPA(pos) to NKX2-5(pos)SIRPA(pos)VCAM1(pos). Up-regulation of VCAM1 was accompanied by the expression of myofilament markers and reduced clonal capacity, implying a restriction of cell fate potential. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. These markers identify specific stages of cardiomyocyte and endothelial lineage commitment and, thus provide a scaffold for establishing a fate map of early human cardiogenesis.
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Rhys J P
authors: RJ
authors: Skelton
authors: Dept. of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors: Magdaline
authors: M
authors: Costa
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
authors: David J
authors: DJ
authors: Anderson
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Freya
authors: F
authors: Bruveris
authors: Monash Institute Pharmaceutical Sciences, Monash University, Parkville, Australia.
authors: Ben W
authors: BW
authors: Finnin
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Katerina
authors: K
authors: Koutsis
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia; Monash Cardiovascular Research Centre, Monash Medical Centre, Clayton, Victoria, Australia.
authors: Deevina
authors: D
authors: Arasaratnam
authors: Monash Cardiovascular Research Centre, Monash Medical Centre, Clayton, Victoria, Australia.
authors: Anthony J
authors: AJ
authors: White
authors: Weill Cornell Medical College in Qatar, Doha, Qatar.
authors: Arash
authors: A
authors: Rafii
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
authors: Elizabeth S
authors: ES
authors: Ng
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia; Dept. of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors: Andrew G
authors: AG
authors: Elefanty
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia; Dept. of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
authors: Edouard G
authors: EG
authors: Stanley
authors: Monash Institute Pharmaceutical Sciences, Monash University, Parkville, Australia.
authors: Colin W
authors: CW
authors: Pouton
authors: Monash Institute Pharmaceutical Sciences, Monash University, Parkville, Australia.
authors: John M
authors: JM
authors: Haynes
authors: Eli and Edythe Broad Stem Cell Research Center, UCLA, USA.
authors: Reza
authors: R
authors: Ardehali
authors: Dept. of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands; Netherlands Proteomics Institute, Leiden, The Netherlands.
authors: Richard P
authors: RP
authors: Davis
authors: Dept. of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands; Netherlands Proteomics Institute, Leiden, The Netherlands.
authors: Christine L
authors: CL
authors: Mummery
authors: Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia; Australian Regenerative Medicine Institute, Monash University, Australia. Electronic address: david.elliott@mcri.edu.au.
authors: David A
authors: DA
authors: Elliott
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D002319:Cardiovascular System / Q000254:growth & development*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D000943:Antigens, Differentiation; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D019010:Vascular Cell Adhesion Molecule-1