title: Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells.
abstract: Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age-related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long-term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin-cleaved OPN attenuates aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. Thus, our data suggest a critical role for reduced stroma-derived OPN for HSC aging and identify thrombin-cleaved OPN as a novel niche informed therapeutic approach for ameliorating HSC phenotypes associated with aging.
authors.affiliation: Institute of Molecular Medicine and Aging Research Center Ulm, University of Ulm, Ulm, Germany.
authors.forename: Novella
authors.initials: N
authors.lastname: Guidi
authors.affiliation: Institute of Molecular Medicine and Aging Research Center Ulm, University of Ulm, Ulm, Germany.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sacma
authors.affiliation: Kompetenzzentrum Ulm Peptide Pharmaceuticals, University of Ulm, Ulm, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Ständker
authors.affiliation: Institute of Molecular Medicine and Aging Research Center Ulm, University of Ulm, Ulm, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Soller
authors.affiliation: Institute of Molecular Medicine and Aging Research Center Ulm, University of Ulm, Ulm, Germany.
authors.forename: Gina
authors.initials: G
authors.lastname: Marka
authors.affiliation: Institute of Molecular Medicine and Aging Research Center Ulm, University of Ulm, Ulm, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Eiwen
authors.affiliation: Department of Dermatology and Allergic Diseases, Universitätsklinikum Ulm, Ulm, Germany.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Weiss
authors.affiliation: Institute of Molecular Virology, Universitätsklinikum Ulm, Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.affiliation: Institute of Organic Chemistry III, University of Ulm, Ulm, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Weil
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Cancelas
authors.affiliation: Institute of Molecular Medicine and Aging Research Center Ulm, University of Ulm, Ulm, Germany.
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Florian
authors.affiliation: Institute of Molecular Medicine and Aging Research Center Ulm, University of Ulm, Ulm, Germany hartmut.geiger@uni-ulm.de.|Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Hartmut
authors.identifier: 0000-0001-7314-9891
authors.initials: H
authors.lastname: Geiger
mesh_terms: D000375:Aging; D000818:Animals; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000378:metabolism*; D010641:Phenotype
chemical_list: C506896:Spp1 protein, mouse; D053495:Osteopontin
keywords: aging; hematopoietic stem cell; microenvironment; niche; osteopontin