| Literature DB >> 24968096 |
Rhys J P Skelton1, Magdaline Costa2, David J Anderson1, Freya Bruveris1, Ben W Finnin3, Katerina Koutsis1, Deevina Arasaratnam4, Anthony J White5, Arash Rafii6, Elizabeth S Ng1, Andrew G Elefanty7, Edouard G Stanley7, Colin W Pouton3, John M Haynes3, Reza Ardehali8, Richard P Davis9, Christine L Mummery9, David A Elliott10.
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.Entities:
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Year: 2014 PMID： 24968096 DOI： 10.1016/j.scr.2014.04.016
Source DB: PubMed Journal: Stem Cell Res ISSN： 1873-5061 Impact factor: 2.020