Functional differences between two Tie2 ligands, angiopoietin-1 and -2, in regulation of adult bone marrow hematopoietic stem cells

Experimental Hematology
Yumiko GomeiFumio Arai

Abstract

Angiopoietin-1 (Ang-1) plays a critical role in the maintenance of hematopoietic stem cells (HSCs) in the bone marrow (BM) through its binding to the Tie2 receptor. Ang-2, another Tie2 ligand, is known to be an antagonist of Tie2/Ang-1 signaling in angiogenesis; however, its function in regulation of HSCs remains unclear. Here, we investigated the functional differences between Ang-1 and Ang-2 in the maintenance of HSCs. We treated mouse BM lineage(-)Sca-1(+)c-Kit(+) side population(+) cells with Ang-1 and/or Ang-2, and evaluated angiopoietin function by gene expression analysis, immunocytochemical staining of phosphorylated Akt, a colony-formation assay, and a long-term BM reconstitution assay. Gene expression analysis and BM transplantation assay revealed that Ang-1 upregulated expression of p57, p18, Itgb1, Alcam, Tie2, Hoxb4, and Bmi1 genes in HSCs, while Ang-2 antagonized the effects of Ang-1. Ang-1 enhanced the phosphorylation of Akt, while Ang-2 again reduced the effect of Ang-1. The colony assay demonstrated that neither Ang-1, nor Ang-2 influenced the colony formation of HSCs. BM transplantation assay, following in vitro cultivation of HSCs with angiopoietins, showed that Ang-1 maintained long-term repopulating activit...Continue Reading

Citations

Jul 14, 2012·PloS One·Ernestina SaulleSimona Coppola
Jun 27, 2013·Experimental Hematology·Huimin CaoSusan K Nilsson
Nov 15, 2012·Biochemical and Biophysical Research Communications·Yoshiko Matsumoto IkushimaToshio Suda
Oct 29, 2011·Biochemical and Biophysical Research Communications·Emi IchiharaKazuhiro Morishita
Feb 24, 2011·Blood·Francesca AguiloHans-Willem Snoeck
Aug 18, 2012·Bone Marrow Research·Kamonnaree Chotinantakul, Wilairat Leeanansaksiri
Nov 11, 2011·Blood·Gerd BungartzStephen G Emerson
Sep 18, 2020·Annals of Biomedical Engineering·Victoria BarnhouseBrendan Harley
Aug 10, 2021·Frontiers in Cell and Developmental Biology·Julia FröbelRobert A J Oostendorp

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