Expandable Arterial Endothelial Precursors From Human CD34 + Cells Differ in Their Proclivity to Undergo an Endothelial-to-Mesenchymal Transition

Stem Cell Reports. 2018 Jan 9;10(1):73-86. doi: 10.1016/j.stemcr.2017.12.011.

Abstract

Arterial diseases continue to pose a major health concern but in vitro studies are limited because explanted cells can exhibit poor proliferative capacity and a loss of specificity. Here, we find that two transcription factors, MYCN and SOX17, induce and indefinitely expand in culture precursors of human arterial endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs are derived from CD34+ cells found in umbilical cord blood or adult bone marrow. Independent eAEP lines differ in their proclivity to undergo an endothelial-to-mesenchymal transition (EndoMT), a hallmark event in a broad array of vascular diseases and disorders. Some cell lines spontaneously become mesenchymal over time in culture, an effect exacerbated by inhibition of the fibroblast growth factor receptor, while others do not readily convert. These distinctions were exploited to identify genes that correlate with resistance to an EndoMT and to elucidate transcriptional changes that underpin the transition.

Keywords: MYCN; SOX17; arterial endothelial precursors; endothelial-to-mesenchymal transition; reprogramming; self-renewal; transcription factors.

Publication types

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

MeSH terms

  • Antigens, CD34 / metabolism*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation*
  • Endothelial Progenitor Cells / cytology
  • Endothelial Progenitor Cells / metabolism*
  • Fetal Blood / cytology
  • Fetal Blood / metabolism*
  • Humans
  • N-Myc Proto-Oncogene Protein / metabolism
  • Organ Specificity
  • SOXF Transcription Factors / metabolism

Substances

  • Antigens, CD34
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • SOX17 protein, human
  • SOXF Transcription Factors