APELIN promotes hematopoiesis from human embryonic stem cells

Qing C Yu; Claire E Hirst; Magdaline Costa; Elizabeth S Ng; Jacqueline V Schiesser; Karin Gertow; Edouard G Stanley; Andrew G Elefanty

doi:10.1182/blood-2011-12-396093

APELIN promotes hematopoiesis from human embryonic stem cells

Blood. 2012 Jun 28;119(26):6243-54. doi: 10.1182/blood-2011-12-396093. Epub 2012 May 18.

Authors

Qing C Yu¹, Claire E Hirst, Magdaline Costa, Elizabeth S Ng, Jacqueline V Schiesser, Karin Gertow, Edouard G Stanley, Andrew G Elefanty

Affiliation

¹ Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Australia.

PMID: 22611158
DOI: 10.1182/blood-2011-12-396093

Abstract

Transcriptional profiling of differentiating human embryonic stem cells (hESCs) revealed that MIXL1-positive mesodermal precursors were enriched for transcripts encoding the G-protein-coupled APELIN receptor (APLNR). APLNR-positive cells, identified by binding of the fluoresceinated peptide ligand, APELIN (APLN), or an anti-APLNR mAb, were found in both posterior mesoderm and anterior mesendoderm populations and were enriched in hemangioblast colony-forming cells (Bl-CFC). The addition of APLN peptide to the media enhanced the growth of embryoid bodies (EBs), increased the expression of hematoendothelial genes in differentiating hESCs, and increased the frequency of Bl-CFCs by up to 10-fold. Furthermore, APLN peptide also synergized with VEGF to promote the growth of hESC-derived endothelial cells. These studies identified APLN as a novel growth factor for hESC-derived hematopoietic and endothelial cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apelin
Apelin Receptors
Cells, Cultured
Embryonic Stem Cells / drug effects*
Embryonic Stem Cells / metabolism
Embryonic Stem Cells / physiology
Endoderm / drug effects
Endoderm / metabolism
Endoderm / physiology
Gene Expression Profiling
Hemangioblasts / drug effects
Hemangioblasts / metabolism
Hemangioblasts / physiology
Hematopoiesis / drug effects*
Hematopoiesis / genetics
Humans
Intercellular Signaling Peptides and Proteins / metabolism
Intercellular Signaling Peptides and Proteins / pharmacology*
Intercellular Signaling Peptides and Proteins / physiology
Mesoderm / cytology
Mesoderm / drug effects
Mesoderm / metabolism
Mesoderm / physiology
Microarray Analysis
Models, Biological
Protein Binding / drug effects
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism
Up-Regulation / drug effects
Up-Regulation / genetics

Substances

APLN protein, human
APLNR protein, human
Apelin
Apelin Receptors
Intercellular Signaling Peptides and Proteins
Receptors, G-Protein-Coupled