Human ESC-derived hemogenic endothelial cells undergo distinct waves of endothelial to hematopoietic transition. Academic Article uri icon

Overview

MeSH

  • Antigens, CD
  • Cadherins
  • Coculture Techniques
  • Feeder Cells
  • Humans
  • Platelet Membrane Glycoprotein IIb

MeSH Major

  • Cell Differentiation
  • Embryonic Stem Cells
  • Endothelial Cells
  • Hematopoietic Stem Cells
  • Transduction, Genetic

abstract

  • Several studies have demonstrated that hematopoietic cells originate from endotheliumin early development; however, the phenotypic progression of progenitor cells during human embryonic hemogenesis is not well described. Here, we define the developmental hierarchy among intermediate populations of hematopoietic progenitor cells (HPCs) derived from human embryonic stem cells (hESCs). We genetically modified hESCs to specifically demarcate acquisition of vascular (VE-cadherin) and hematopoietic (CD41a) cell fate and used this dual-reporting transgenic hESC line to observe endothelial to hematopoietic transition by real-time confocal microscopy. Live imaging and clonal analyses revealed a temporal bias in commitment of HPCs that recapitulates discrete waves of lineage differentiation noted during mammalian hemogenesis. Specifically, HPCs isolated at later time points showed reduced capacity to form erythroid/ megakaryocytic cells and exhibited a tendency toward myeloid fate that was enabled by expression of the Notch ligand Dll4 on hESC-derived vascular feeder cells. These data provide a framework for defining HPC lineage potential, elucidate a molecular contribution from the vascular niche in promoting hematopoietic lineage progression, and distinguish unique subpopulations of hemogenic endothelium during hESC differentiation. Live imaging of endothelial to hematopoietic conversion identifies distinct subpopulations of hESC-derived hemogenic endothelium. Expression of the Notch ligand DII4 on vascular ECs drives induction of myeloid fate from hESC-derived hematopoietic progenitors.

publication date

  • January 31, 2013

has subject area

  • Antigens, CD
  • Cadherins
  • Cell Differentiation
  • Coculture Techniques
  • Embryonic Stem Cells
  • Endothelial Cells
  • Feeder Cells
  • Hematopoietic Stem Cells
  • Humans
  • Platelet Membrane Glycoprotein IIb
  • Transduction, Genetic

Research

keywords

  • Clinical Trial
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1182/blood-2012-07-444208

PubMed ID

  • 23169780

Additional Document Info

start page

  • 770

end page

  • 780

volume

  • 121

number

  • 5