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

  • Author(s): Skelton, RJP
  • Costa, M
  • Anderson, DJ
  • Bruveris, F
  • Finnin, BW
  • Koutsis, K
  • Arasaratnam, D
  • White, AJ
  • Rafii, A
  • Ng, ES
  • Elefanty, AG
  • Stanley, EG
  • Pouton, CW
  • Haynes, JM
  • Ardehali, R
  • Davis, RP
  • Mummery, CL
  • Elliott, DA
  • et al.

Published Web Location

http://www.ncbi.nlm.nih.gov/pubmed/24968096
No data is associated with this publication.
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. © 2014.

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