Human ESC-derived hemogenic endothelial cells undergo distinct waves of endothelial to hematopoietic transition

Shahin Rafii, Christopher C. Kloss, Jason M. Butler, Michael Ginsberg, Eric Gars, Raphael Lis, Qiansheng Zhan, Pavle Josipovic, Bi Sen Ding, Jenny Xiang, Olivier Elemento, Nikica Zaninovic, Zev Rosenwaks, Michel Sadelain, Arash Rafii Tabrizi, Daylon James

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60 Citations (Scopus)

Abstract

Several studies have demonstrated that hematopoietic cells originate from endothelium in 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.

Original languageEnglish
Pages (from-to)770-780
Number of pages11
JournalBlood
Volume121
Issue number5
DOIs
Publication statusPublished - 31 Jan 2013
Externally publishedYes

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Keywords

  • Expression of the Notch ligand DII4 on vascular ECs drives induction of myeloid fate from hESC-derived hematopoietic progenitors
  • Live imaging of endothelial to hematopoietic conversion identifies distinct subpopulations of hESC-derived hemogenic endothelium

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Rafii, S., Kloss, C. C., Butler, J. M., Ginsberg, M., Gars, E., Lis, R., Zhan, Q., Josipovic, P., Ding, B. S., Xiang, J., Elemento, O., Zaninovic, N., Rosenwaks, Z., Sadelain, M., Tabrizi, A. R., & James, D. (2013). Human ESC-derived hemogenic endothelial cells undergo distinct waves of endothelial to hematopoietic transition. Blood, 121(5), 770-780. https://doi.org/10.1182/blood-2012-07-444208