Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size

By S. Stier, Y. Ko, R. Forkert, C. Lutz, T. Neuhaus, E. Grünewald, T. Cheng, D. Dombkowski, L. Calvi, S. Rittling and 1 more. Journal of Experimental Medicine, 2005

707 citations recorded by the source corpus.

Stem cells reside in a specialized niche that regulates their abundance and fate. Components of the niche have generally been defined in terms of cells and signaling pathways. We define a role for a matrix glycoprotein, osteopontin (OPN), as a constraining factor on hematopoietic stem cells within the bone marrow microenvironment. Osteoblasts that participate in the niche produce varying amounts of OPN in response to stimulation. Using studies that combine OPN-deficient mice and exogenous OPN, we demonstrate that OPN modifies primitive hematopoietic cell number and function in a stem cell–nonautonomous manner. The OPN-null microenvironment was sufficient to increase the number of stem cells associated with increased stromal Jagged1 and Angiopoietin-1 expression and reduced primitive hematopoietic cell apoptosis. The activation of the stem cell microenvironment with parathyroid hormone induced a superphysiologic increase in stem cells in the absence of OPN. Therefore, OPN is a negative regulatory element of the stem cell niche that limits the size of the stem cell pool and may provide a mechanism for restricting excess stem cell expansion under conditions of niche stimulation.

Subfields: Genetics, Oncology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/2474309d887bb06f7a3404b64e79d48ef90aada4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. P. Frenette
2. D. Scadden
3. S. Shi
4. Melinda Larsen
5. William P. Daley
6. Sarah B. Peters
7. W. Sonoyama
8. Aviv Bergman

In Oncology

1. D. Scadden
2. S. Shi
3. Melinda Larsen
4. William P. Daley
5. Sarah B. Peters

In Rheumatology

1. S. Shi

Citations in the corpus

• Mesenchymal stem cells in health and disease (2008, background): “Here, stromal cells contribute to the generation of the niche by regulating the size of the pool of HSCs and by providing signals necessary to maintain HSCs in a non-proliferating state and refractory to differentiation stimuli, but also to support HSC survival through trophic and anti-apoptotic mol”
• The stem-cell niche as an entity of action (2006, background): “Third, another matrix protein, the Arg–Gly–Asp (RGD)-containing sialoprotein, osteopontin (OPN), has now been demonstrated to contribute to HS-cell regulatio”
• Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche (2007, background): “For example, ECM proteins, such as tenascin C, osteopontin and the combination of Bgn and decorin, have been found to control the number of neural stem cells, hematopoietic stem cells and BMSCs, respectivel”
• Extracellular matrix dynamics in development and regenerative medicine (2008, background): “the stem cell niche to suppress stem cell expansion (Nilsson et al., 2005; Stier et al., 2005).”