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Estrogen deficiency expands hemopoietic stem and progenitor cells (HSPCs) and mature blood lineages, but the involved mechanism and the affected HSPC populations are mostly unknown. Here we show that ovariectomy (ovx) expands short-term HSPCs (ST-HSPCs) and improves blood cell engraftment and host survival after bone marrow (BM) transplantation through a dual role of the T-cell costimulatory molecule CD40 ligand (CD40L). This surface receptor is required for ovx to stimulate T-cell production of Wnt10b, a Wnt ligand that activates Wnt signaling in HSPCs and stromal cells (SCs). Moreover, CD40L is required for ovx to increase SC production of the hemopoietic cytokines interleukin (IL)-6, IL-7, and granulocyte macrophage-colony-stimulating factor. Attesting to the relevance of CD40L and Wnt10b, ovx fails to expand ST-HSPCs in CD40L-null mice and in animals lacking global or T-cell expression of Wnt10b. In summary, T cells expressed CD40L, and the resulting increased production of WntlOb and hemopoietic cytokines by T cells and SCs, respectively, plays a pivotal role in the may represent pharmacological targets mechanism by which ovx regulates hemopoiesis. The data suggest that antiestrogens to improve ST-HSPC function through activation of the microenvironment. [ABSTRACT FROM AUTHOR]

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 (ST-HSPCs) and Improve blood cell engraftment and host survival after BM transplantation. Silencing of PTH/PIH-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 I cells may provide pharmacologic targets for HSPC expansion. [ABSTRACT FROM AUTHOR]