SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development

Rhys J P Skelton, Magdaline Costa, David John Anderson, Freya Bruveris, Ben W Finnin, Katerina Koutsis, Deevina Arasaratnam, Anthony John White, Arash Rafii, Elizabeth Siew-Sun Ng, Andrew G Elefanty, Edouard G Stanley, Colin W Pouton, John M Haynes, Reza Ardehali, Richard P Davis, Christine L Mummery, David A Elliott

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38 Citations (Scopus)

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 NKX2-5GFP was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5GFP/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 NKX2-5posCD34pos 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 NKX2-5posSIRPApos to NKX2-5posSIRPAposVCAM1pos. 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.
Original languageEnglish
Pages (from-to)172 - 179
Number of pages8
JournalStem Cell Research
Volume13
Issue number1
DOIs
Publication statusPublished - 2014

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