Functional Heterogeneity of Endothelial Cells Derived from Human Pluripotent Stem Cells

Saritha S D'Souza, Akhilesh Kumar, Igor I Slukvin

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Specification of endothelial cells (ECs) into arterial, venous, and lymphatic cells is a crucial process of vascular development, and expanding our knowledge about EC specification from human pluripotent stem cells (hPSCs) will aid the design of optimal strategies for producing desired types of ECs for therapies. In our prior studies, we revealed that hPSC-derived VE-cadherin(V)+CD31+CD34+ ECs are heterogeneous and include at least three major subsets with distinct hemogenic properties: V+CD43/235a-CD73- hemogenic endothelial progenitors (HEPs), V+CD43loCD235a+73- angiogenic hematopoietic progenitors (AHPs), and V+CD43/235a-73+ non-HEPs. In this study, using angiogenesis assays, we demonstrated that ECs within these subsets have distinct endothelial colony- and tube-forming properties, proliferative and migratory properties, and endothelial nitric oxide synthase and inflammatory cytokine production potentials. Culture of isolated subsets in arterial, venous, and lymphatic conditions revealed that AHPs are skewed toward lymphatic, HEPs toward arterial, and non-HEPs toward venous differentiation in vitro. These findings suggest that selection and enhancement of production of a particular EC subset may aid in generating desirable EC populations with arterial, venous, or lymphatic properties from hPSCs.

Original languageEnglish (US)
Pages (from-to)524-533
Number of pages10
JournalStem Cells and Development
Issue number8
StatePublished - Apr 15 2018
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Dr. Toru Nakano for providing OP9 cells, Mitch Probasco for cell sorting, and Mathew Raymond for editorial assistance. This work was supported by funds from the National Institutes of Health (U01HL099773, U01HL134655, P51 RR000167) and the Charlotte Geyer Foundation.

Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc. 2018.


  • Antigens, CD/genetics
  • Antigens, CD34/genetics
  • Biomarkers/metabolism
  • Cadherins/genetics
  • Cell Differentiation
  • Cell Line
  • Cell Lineage/physiology
  • Cell Movement
  • Cell Proliferation
  • Colony-Forming Units Assay
  • Cytokines/genetics
  • Gene Expression
  • Hemangioblasts/cytology
  • Humans
  • Leukosialin/genetics
  • Neovascularization, Physiologic
  • Nitric Oxide Synthase Type III/genetics
  • Platelet Endothelial Cell Adhesion Molecule-1/genetics
  • Pluripotent Stem Cells/cytology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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