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

被引：35

作者：

Li, Jau-Yi

Adams, Jonathan

Calvi, Laura M. ^{[2
]}

Lane, Timothy F. ^{[3
,4
,5
]}

DiPaolo, Richard ^{[6
]}

Weitzmann, M. Neale ^{[7
]}

Pacifici, Roberto ^{[1
,8
]}

机构：

[1] Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Dept Med, Atlanta, GA 30322 USA

[2] Univ Rochester, Dept Med, Endocrine Div, Rochester, NY USA

[3] Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA 90024 USA

[4] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90024 USA

[5] Univ Calif Los Angeles, Orthoped Hosp Res Ctr, Los Angeles, CA 90024 USA

[6] St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO USA

[7] Atlanta Vet Adm Med Ctr, Decatur, GA USA

[8] Emory Univ, Immunol & Mol Pathogenesis Program, Atlanta, GA 30322 USA

来源：

BLOOD | 2012年 / 120卷 / 22期

基金：

美国国家卫生研究院;

关键词：

PARATHYROID-HORMONE; SELF-RENEWAL; GENE-EXPRESSION; BETA-CATENIN; IN-VIVO; ANABOLIC ACTIVITY; PROGENITOR CELLS; RECEPTOR; NOTCH; IDENTIFICATION;

D O I：

10.1182/blood-2012-06-438531

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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/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 ST-HSPCs 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. (Blood. 2012;120(22):4352-4362)

引用

页码：4352 / 4362

页数：11

共 49 条

[21] The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells [J].