An expandable, inducible hemangioblast state regulated by fibroblast growth factor

Stem Cell Reports. 2014 Dec 9;3(6):1043-57. doi: 10.1016/j.stemcr.2014.10.003. Epub 2014 Nov 13.

Abstract

During development, the hematopoietic and vascular lineages are thought to descend from common mesodermal progenitors called hemangioblasts. Here we identify six transcription factors, Gata2, Lmo2, Mycn, Pitx2, Sox17, and Tal1, that "trap" murine cells in a proliferative state and endow them with a hemangioblast potential. These "expandable" hemangioblasts (eHBs) are capable, once released from the control of the ectopic factors, to give rise to functional endothelial cells, multilineage hematopoietic cells, and smooth muscle cells. The eHBs can be derived from embryonic stem cells, from fetal liver cells, or poorly from fibroblasts. The eHBs reveal a central role for fibroblast growth factor, which not only promotes their expansion, but also facilitates their ability to give rise to endothelial cells and leukocytes, but not erythrocytes. This study serves as a demonstration that ephemeral progenitor states can be harnessed in vitro, enabling the creation of tractable progenitor cell lines.

Publication types

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

MeSH terms

  • Animals
  • Blood Cells / cytology
  • Blood Cells / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Gene Expression Profiling
  • Hemangioblasts / cytology*
  • Hemangioblasts / drug effects
  • Hemangioblasts / metabolism*
  • High-Throughput Nucleotide Sequencing
  • Immunophenotyping
  • Mice
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism
  • Phenotype
  • Transcriptome

Substances

  • Fibroblast Growth Factors

Associated data

  • GEO/GSE60896