The expression of Sox17 identifies and regulates haemogenic endothelium

Nat Cell Biol. 2013 May;15(5):502-10. doi: 10.1038/ncb2724. Epub 2013 Apr 21.

Abstract

Although it is well recognized that haematopoietic stem cells (HSCs) develop from a specialized population of endothelial cells known as haemogenic endothelium, the regulatory pathways that control this transition are not well defined. Here we identify Sox17 as a key regulator of haemogenic endothelial development. Analysis of Sox17-GFP reporter mice revealed that Sox17 is expressed in haemogenic endothelium and emerging HSCs and that it is required for HSC development. Using the mouse embryonic stem cell differentiation model, we show that Sox17 is also expressed in haemogenic endothelium generated in vitro and that it plays a pivotal role in the development and/or expansion of haemogenic endothelium through the Notch signalling pathway. Taken together, these findings position Sox17 as a key regulator of haemogenic endothelial and haematopoietic development.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Embryonic Development
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Developmental*
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HMGB Proteins / genetics
  • HMGB Proteins / metabolism*
  • Hemangioblasts / cytology*
  • Hemangioblasts / metabolism
  • Hematopoiesis
  • Luciferases / metabolism
  • Male
  • Mice
  • Nucleotide Motifs
  • Promoter Regions, Genetic
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism
  • SOXF Transcription Factors / genetics
  • SOXF Transcription Factors / metabolism*
  • Signal Transduction
  • Transfection

Substances

  • HMGB Proteins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • SOXF Transcription Factors
  • Sox17 protein, mouse
  • Sox18 protein, mouse
  • Green Fluorescent Proteins
  • Luciferases