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

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 t...

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Autores principales: Stier, Sebastian, Ko, Yon, Forkert, Randolf, Lutz, Christoph, Neuhaus, Thomas, Grünewald, Elisabeth, Cheng, Tao, Dombkowski, David, Calvi, Laura M., Rittling, Susan R., Scadden, David T.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213260/
https://www.ncbi.nlm.nih.gov/pubmed/15928197
http://dx.doi.org/10.1084/jem.20041992
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author Stier, Sebastian
Ko, Yon
Forkert, Randolf
Lutz, Christoph
Neuhaus, Thomas
Grünewald, Elisabeth
Cheng, Tao
Dombkowski, David
Calvi, Laura M.
Rittling, Susan R.
Scadden, David T.
author_facet Stier, Sebastian
Ko, Yon
Forkert, Randolf
Lutz, Christoph
Neuhaus, Thomas
Grünewald, Elisabeth
Cheng, Tao
Dombkowski, David
Calvi, Laura M.
Rittling, Susan R.
Scadden, David T.
author_sort Stier, Sebastian
collection PubMed
description 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.
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spelling pubmed-22132602008-03-11 Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size Stier, Sebastian Ko, Yon Forkert, Randolf Lutz, Christoph Neuhaus, Thomas Grünewald, Elisabeth Cheng, Tao Dombkowski, David Calvi, Laura M. Rittling, Susan R. Scadden, David T. J Exp Med Article 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. The Rockefeller University Press 2005-06-06 /pmc/articles/PMC2213260/ /pubmed/15928197 http://dx.doi.org/10.1084/jem.20041992 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Stier, Sebastian
Ko, Yon
Forkert, Randolf
Lutz, Christoph
Neuhaus, Thomas
Grünewald, Elisabeth
Cheng, Tao
Dombkowski, David
Calvi, Laura M.
Rittling, Susan R.
Scadden, David T.
Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size
title Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size
title_full Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size
title_fullStr Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size
title_full_unstemmed Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size
title_short Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size
title_sort osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213260/
https://www.ncbi.nlm.nih.gov/pubmed/15928197
http://dx.doi.org/10.1084/jem.20041992
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