Axin2/Conductin Is Required for Normal Haematopoiesis and T Lymphopoiesis

Jolanda J D de Roo, Amiet Chhatta, Laura Garcia-Perez, Brigitta A E Naber, Sandra A Vloemans, Daniela C F Salvatori, Karin Pike-Overzet, Harald Mikkers, Frank J T Staal*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The development of T lymphocytes in the thymus and their stem cell precursors in the bone marrow is controlled by Wnt signaling in strictly regulated, cell-type specific dosages. In this study, we investigated levels of canonical Wnt signaling during hematopoiesis and T cell development within the Axin2-mTurquoise2 reporter. We demonstrate active Wnt signaling in hematopoietic stem cells (HSCs) and early thymocytes, but also in more mature thymic subsets and peripheral T lymphocytes. Thymic epithelial cells displayed particularly high Wnt signaling, suggesting an interesting crosstalk between thymocytes and thymic epithelial cells (TECs). Additionally, reporter mice allowed us to investigate the loss of Axin2 function, demonstrating decreased HSC repopulation upon transplantation and the partial arrest of early thymocyte development in Axin2Tg/Tg full mutant mice. Mechanistically, loss of Axin2 leads to supraphysiological Wnt levels that disrupt HSC differentiation and thymocyte development.

Original languageEnglish
Article number2679
Pages (from-to)1-16
JournalCells
Volume11
Issue number17
DOIs
Publication statusPublished - 1 Sept 2022

Keywords

  • Animals
  • Axin Protein/genetics
  • Cell Differentiation
  • Hematopoiesis/genetics
  • Hematopoietic Stem Cells
  • Lymphopoiesis/genetics
  • Mice
  • Wnt Signaling Pathway
  • WNT- thymus-hematopoietic stem cell

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