PTH expands short-term murine hemopoietic stem cells through T cells

Jau Yi Li, Jonathan Adams, Laura M. Calvi, Timothy F Lane, Richard DiPaolo, M. Neale Weitzmann, Roberto Pacifici*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Intermittent parathyroid hormone (iPTH) treatment expands hemopoietic stem and progenitor cells (HSPCs), but the involved mechanisms and the affected HSPC populations are mostly unknown. Here we show that T cells are required for iPTH to expand short-term HSPCs (STHSPCs) and improve blood cell engraftment and host survival after BM transplantation. Silencing of PTH/PTH-related protein receptor (PPR) in T cells abrogates the effects of iPTH, thus demonstrating a requirement for direct PPR signaling in T cells. Mechanistically, iPTH expands ST-HSPCs by activating Wnt signaling in HSPCs and stromal cells (SCs) through T-cell production of the Wnt ligand Wnt10b. Attesting to the relevance of Wnt10b, iPTH fails to expand STHSPCs in mice with Wnt10b-/- T cells. Moreover, iPTH fails to promote engraftment and survival after BM transplantation in Wnt10b null mice. In summary, direct PPR signaling in T cells and the resulting production of Wnt10b play a pivotal role in the mechanism by which iPTH expands ST-HSPCs. The data suggest that T cells may provide pharmacologic targets for HSPC expansion.

Original languageEnglish (US)
Pages (from-to)4352-4362
Number of pages11
JournalBlood
Volume120
Issue number22
DOIs
StatePublished - Nov 22 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Li, J. Y., Adams, J., Calvi, L. M., Lane, T. F., DiPaolo, R., Weitzmann, M. N., & Pacifici, R. (2012). PTH expands short-term murine hemopoietic stem cells through T cells. Blood, 120(22), 4352-4362. https://doi.org/10.1182/blood-2012-06-438531