SHIP1-expressing mesenchymal stem cells regulate hematopoietic stem cell homeostasis and lineage commitment during aging

• Published in: Stem cells and development Vol. 24; no. 9; p. 1073
• Main Authors: Iyer, Sonia, Brooks, Robert, Gumbleton, Matthew, Kerr, William G
• Format: Journal Article
• Language: English
• Published: United States 01.05.2015
• Subjects: Aging - blood; Animals; Cell Lineage; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Homeostasis; Inositol Polyphosphate 5-Phosphatases; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mice; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Phosphoric Monoester Hydrolases - deficiency; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Stem Cell Niche
• ISSN: 1557-8534
• DOI: 10.1089/scd.2014.0501

Hematopoietic stem cell (HSC) self-renewal and lineage choice are subject to intrinsic control. However, this intrinsic regulation is also impacted by external cues provided by niche cells. There are multiple cellular components that participate in HSC support with the mesenchymal stem cell (MSC) playing a pivotal role. We had previously identified a role for SH2 domain-containing inositol 5'-phosphatase-1 (SHIP1) in HSC niche function through analysis of mice with germline or induced SHIP1 deficiency. In this study, we show that the HSC compartment expands significantly when aged in a niche that contains SHIP1-deficient MSC; however, this expanded HSC compartment exhibits a strong bias toward myeloid differentiation. In addition, we show that SHIP1 prevents chronic G-CSF production by the aging MSC compartment. These findings demonstrate that intracellular signaling by SHIP1 in MSC is critical for the control of HSC output and lineage commitment during aging. These studies increase our understanding of how myeloid bias occurs in aging and thus could have implications for the development of myeloproliferative disease in aging.