Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging

Abstract In adult mammals, hematopoietic stem cells (HSCs) reside in the bone marrow and are in part regulated by the bone marrow microenvironment, called the stem cell niche. We have previously identified the bone marrow morphogen osteopontin (OPN), which is abundantly present in the bone marrow ex...

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Autores principales:	Jin Li, Carmen Carrillo García, Tamara Riedt, Maria Brandes, Sabrina Szczepanski, Peter Brossart, Wolfgang Wagner, Viktor Janzen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/93d4e381f0564c5887c266bef7a8792f
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spelling	oai:doaj.org-article:93d4e381f0564c5887c266bef7a8792f2021-12-02T15:07:58ZMurine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging10.1038/s41598-018-21324-x2045-2322https://doaj.org/article/93d4e381f0564c5887c266bef7a8792f2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21324-xhttps://doaj.org/toc/2045-2322Abstract In adult mammals, hematopoietic stem cells (HSCs) reside in the bone marrow and are in part regulated by the bone marrow microenvironment, called the stem cell niche. We have previously identified the bone marrow morphogen osteopontin (OPN), which is abundantly present in the bone marrow extracellular matrix, as a negative regulator of the size of the HSC pool under physiological conditions. Here, we study the impact of OPN on HSC function during aging using an OPN-knockout mouse model. We show that during aging OPN deficiency is associated with an increase in lymphocytes and a decline in erythrocytes in peripheral blood. In a bone marrow transplantation setting, aged OPN-deficient stem cells show reduced reconstitution ability likely due to insufficient differentiation of HSCs into more mature cells. In serial bone marrow transplantation, aged OPN−/− bone marrow cells fail to adequately reconstitute red blood cells and platelets, resulting in severe anemia and thrombocytopenia as well as premature deaths of recipient mice. Thus, OPN has different effects on HSCs in aged and young animals and is particularly important to maintain stem cell function in aging mice.Jin LiCarmen Carrillo GarcíaTamara RiedtMaria BrandesSabrina SzczepanskiPeter BrossartWolfgang WagnerViktor JanzenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jin Li Carmen Carrillo García Tamara Riedt Maria Brandes Sabrina Szczepanski Peter Brossart Wolfgang Wagner Viktor Janzen Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging
description	Abstract In adult mammals, hematopoietic stem cells (HSCs) reside in the bone marrow and are in part regulated by the bone marrow microenvironment, called the stem cell niche. We have previously identified the bone marrow morphogen osteopontin (OPN), which is abundantly present in the bone marrow extracellular matrix, as a negative regulator of the size of the HSC pool under physiological conditions. Here, we study the impact of OPN on HSC function during aging using an OPN-knockout mouse model. We show that during aging OPN deficiency is associated with an increase in lymphocytes and a decline in erythrocytes in peripheral blood. In a bone marrow transplantation setting, aged OPN-deficient stem cells show reduced reconstitution ability likely due to insufficient differentiation of HSCs into more mature cells. In serial bone marrow transplantation, aged OPN−/− bone marrow cells fail to adequately reconstitute red blood cells and platelets, resulting in severe anemia and thrombocytopenia as well as premature deaths of recipient mice. Thus, OPN has different effects on HSCs in aged and young animals and is particularly important to maintain stem cell function in aging mice.
format	article
author	Jin Li Carmen Carrillo García Tamara Riedt Maria Brandes Sabrina Szczepanski Peter Brossart Wolfgang Wagner Viktor Janzen
author_facet	Jin Li Carmen Carrillo García Tamara Riedt Maria Brandes Sabrina Szczepanski Peter Brossart Wolfgang Wagner Viktor Janzen
author_sort	Jin Li
title	Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging
title_short	Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging
title_full	Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging
title_fullStr	Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging
title_full_unstemmed	Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging
title_sort	murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/93d4e381f0564c5887c266bef7a8792f
work_keys_str_mv	AT jinli murinehematopoieticstemcellreconstitutionpotentialismaintainedbyosteopontinduringaging AT carmencarrillogarcia murinehematopoieticstemcellreconstitutionpotentialismaintainedbyosteopontinduringaging AT tamarariedt murinehematopoieticstemcellreconstitutionpotentialismaintainedbyosteopontinduringaging AT mariabrandes murinehematopoieticstemcellreconstitutionpotentialismaintainedbyosteopontinduringaging AT sabrinaszczepanski murinehematopoieticstemcellreconstitutionpotentialismaintainedbyosteopontinduringaging AT peterbrossart murinehematopoieticstemcellreconstitutionpotentialismaintainedbyosteopontinduringaging AT wolfgangwagner murinehematopoieticstemcellreconstitutionpotentialismaintainedbyosteopontinduringaging AT viktorjanzen murinehematopoieticstemcellreconstitutionpotentialismaintainedbyosteopontinduringaging
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Murine hematopoietic stem cell reconstitution potential is maintained by osteopontin during aging

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