CX3CL1/CX3CR1-signalling in the CD9/S100β/SOX2-positive adult pituitary stem/progenitor cells modulates differentiation into endothelial cells

Histochem Cell Biol. 2020 Jun;153(6):385-396. doi: 10.1007/s00418-020-01862-0. Epub 2020 Mar 9.

Abstract

Approximately 8% of CD9-, S100β- and SOX2-triple positive (CD9/S100β/SOX2-positive) stem/progenitor cells in the anterior lobe of the rat pituitary gland have previously been shown to differentiate into endothelial cells in vitro, suggesting that they play a role in vascularisation as tissue-resident vascular precursor cells. In the present study, we focused on chemokine ligands to further characterise the CD9/S100β/SOX2-positive cells and found that they distinctively express CX3C chemokine ligand 1 (Cx3cl1). Immunohistochemical analysis of the anterior lobe showed that CX3CL1-positive cells comprised 7.8% in CD9-positive cells. By cultivation of the CD9-positive cells on laminin-coated plates, we observed that the expression levels of Cx3cl1 decreased, while those of Sox18, an endothelial cell-progenitor marker, and Cx3cr1, a CX3CL1 receptor, increased. Furthermore, in a rat model of prolactinoma, the most common pituitary tumour, which is accompanied by frequent neo-vasculogenesis in the anterior lobe, we have confirmed a decrease in Cx3cl1 expression and an increase in Cx3cr1 expression, as well as a prominent increase in Sox18 expression. These findings suggest that CX3CL1/CX3CR1 signalling in CD9/S100β/SOX2-positive cells plays an important role in resupplying endothelial cells for vascular remodelling in the anterior lobe.

Keywords: CX3CL1; CX3CR1; Cluster of differentiation 9; Pituitary; Stem/progenitor cell.

MeSH terms

  • Animals
  • CX3C Chemokine Receptor 1 / metabolism*
  • Cell Differentiation
  • Chemokine CX3CL1 / metabolism*
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Male
  • Pituitary Gland / cytology*
  • Pituitary Gland / metabolism
  • Rats
  • Rats, Inbred F344
  • Rats, Wistar
  • S100 Calcium Binding Protein beta Subunit / metabolism*
  • SOXB1 Transcription Factors / metabolism*
  • Signal Transduction / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Tetraspanin 29 / metabolism*

Substances

  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, rat
  • Chemokine CX3CL1
  • Cx3cl1 protein, rat
  • S100 Calcium Binding Protein beta Subunit
  • SOXB1 Transcription Factors
  • Sox2 protein, rat
  • Tetraspanin 29