| 1. |
- Karlsson, Göran, et al.
(författare)
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The Tetraspanin CD9 Affords High-Purity Capture of All Murine Hematopoietic Stem Cells
- 2013
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 4:4, s. 642-648
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Tidskriftsartikel (refereegranskat)abstract
- Prospective isolation is critical for understanding the cellular and molecular aspects of stem cell heterogeneity. Here, we identify the cell surface antigen CD9 as a positive marker that provides a simple alternative for hematopoietic stem cell isolation at high purity. Crucially, CD9 affords the capture of all hematopoietic stem cells in murine bone marrow in the absence of contaminating populations that lack authentic stem cell function. Using CD9 as a tool to subdivide hematopoietic stem-cell-containing populations, we provide evidence for heterogeneity at the cellular, functional, and molecular levels.
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| 2. |
- Miharada, Kenichi, et al.
(författare)
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Cripto Regulates Hematopoietic Stem Cells as a Hypoxic-Niche-Related Factor through Cell Surface Receptor GRP78.
- 2011
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 9:4, s. 330-344
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cells (HSCs) are maintained in hypoxic niches in endosteal regions of bones. Here we demonstrate that Cripto and its receptor GRP78 are important regulators of HSCs in the niche. Flow cytometry analyses revealed two distinct subpopulations of CD34(-)KSL cells based on the expression of GRP78, and these populations showed different reconstitution potential in transplantation assays. GRP78(+)HSCs mainly reside in the endosteal area, are more hypoxic, and exhibit a lower mitochondrial potential, and their HSC capacity was maintained in vitro by Cripto through induction of higher glycolytic activity. Additionally, HIF-1α KO mice have decreased numbers of GRP78(+)HSCs and reduced expression of Cripto in the endosteal niche. Furthermore, blocking GRP78 induced a movement of HSCs from the endosteal to the central marrow area. These data suggest that Cripto/GRP78 signaling is an important pathway that regulates HSC quiescence and maintains HSCs in hypoxia as an intermediary of HIF-1α.
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| 3. |
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| 4. |
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| 5. |
- Miharada, Kenichi, et al.
(författare)
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Hematopoietic stem cells are regulated by Cripto, as an intermediary of HIF-1α in the hypoxic bone marrow niche.
- 2012
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1266:1, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- Cripto has been known as an embryonic stem (ES)- or tumor-related soluble/cell membrane protein. In this study, we demonstrated that Cripto has a role as an important regulatory factor for hematopoietic stem cells (HSCs). Recombinant Cripto sustained the reconstitution ability of HSCs in vitro. Flow cytometry analysis uncovered that GRP78, one of the candidate receptors for Cripto, was expressed on a subset of HSCs and could distinguish dormant/myeloid-biased HSCs and active/lymphoid-biased HSCs. Cripto is expressed in hypoxic endosteal niche cells where GRP78(+) HSCs mainly reside. Proteomics analysis revealed that Cripto-GRP78 binding stimulates glycolytic metabolism-related proteins and results in lower mitochondrial potential in HSCs. Furthermore, conditional knockout mice for HIF-1α, a master regulator of hypoxic responses, showed reduced Cripto expression and decreased GRP78(+) HSCs in the endosteal niche area. Thus, Cripto-GRP78 is a novel HSC regulatory signal mainly working in the hypoxic niche.
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| 6. |
- Rörby, Emma, et al.
(författare)
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Human hematopoietic stem/progenitor cells overexpressing Smad4 exhibit impaired reconstitution potential in vivo.
- 2012
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 120, s. 4343-4351
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cells (HSCs) constitute a rare population of tissue-specific cells that can self-renew and differentiate into all lineages of the blood cell system. These properties are critical for tissue regeneration and clinical applications of HSCs. Cord blood is an easily accessible source of HSCs. However, the number of HSCs from one unit is too low to effectively transplant most adult patients, and expansion of HSCs in vitro has met with limited success due to incomplete knowledge regarding mechanisms regulating self-renewal. Members of the transforming growth factor-β (TGF-β) superfamily have been shown to regulate HSCs through the Smad signaling pathway, however, its role in human HSCs has remained relatively uncharted in vivo. Therefore, we asked whether enforced expression of the common-Smad, Smad4, could reveal a role for TGF-β in human hematopoietic stem/progenitor cells (HSPCs) from cord blood. Using a lentiviral overexpression approach, we demonstrate that Smad4 overexpression sensitizes HSPCs to TGF-β, resulting in growth arrest and apoptosis in vitro. This phenotype translates in vivo into reduced HSPC reconstitution capacity yet intact lineage distribution. This suggests that the Smad pathway regulates self-renewal independently of differentiation. These findings demonstrate that the Smad signaling circuitry negatively regulates the regeneration capacity of human HSPCs in vivo.
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| 7. |
- Salomonsson, Emma, et al.
(författare)
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Mutational tuning of galectin-3 specificity and biological function.
- 2010
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 285, s. 35079-35091
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Tidskriftsartikel (refereegranskat)abstract
- Galectins are defined by a conserved beta-galactoside binding site, which has been linked to many of their important functions in e.g. cell adhesion, signaling and intracellular trafficking. Weak adjacent sites may enhance or decrease affinity for natural beta-galactoside containing glycoconjugates, but little is known about the biological role of this modulation of affinity (fine specificity). We have now produced 10 mutants of human galectin-3, with changes in these adjacent sites, which have altered carbohydrate-binding fine specificity but which retain the basic beta-galactoside binding activity as show by glycan-array binding and a solution-based fluorescence anisotropy assay. Each mutant was also tested in two biological assays to provide a correlation between fine specificity and function. Galectin-3 R186S, which has selectively lost affinity for LacNAc, a disaccharide moiety commonly found on glycoprotein glycans, has lost the ability to activate neutrophil leukocytes and intracellular targeting into vesicles. K176L has increased affinity for beta-galactosides substituted with GlcNAcbeta1-3 as found in poly-N-acetyllactosaminoglycans, and increased potency to activate neutrophil leukocytes, even though it has lost other aspects of galectin-3 fine specificity. G182A has altered carbohydrate-binding fine specificity and altered intracellular targeting into vesicles, a possible link to the intracellular galectin-3-mediated anti-apoptotic effect known to be lost by this mutant. Finally, the mutants have helped to define the differences in fine specificity shown by Xenopus, mouse and human galectin-3 and as such, evidence for adaptive change during evolution.
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| 10. |
- Atarijabarzadeh, Sevil, et al.
(författare)
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Biofilm formation on silicone materials containing various antimicrobial agents
- 2010
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Konferensbidrag (refereegranskat)abstract
- The colonisation of microorganisms and subsequent biofilm formation on the surface of polymeric high voltage insulators affect the surface properties and can lead to failure of the insulators. In this study, silicone materials were prepared with different antimicrobial agents. The materials were analysed for the changes in the physical, chemical, surface and mechanical properties before and after biological growth test. Microorganisms used for the biological tests were fungi defined in the international standard test ISO 846 for electrical applications (Aspergillus niger van Tieghem, Penicillium funiculosum Thom, Paecilomyces variotii Bainier, Chaetomium globosum Kunze: Fries, Aspergillus terreus Thom, Aureobasidium pullulans (de Bary) Arnaud & Penicillium ochrochloron Biourge) and algae isolated from insulators in Sri Lanka and Tanzania (Chlorella vulgaris var. Autotrophica + various bacterial strains). Fungi growth test was performed by inoculation of the fungi on the surface of the materials and incubation in an oven at 28°C and 98% humidity for a specific period. Algae growth test was performed by inoculation on the material surface and subsequent incubation in room temperature under a constant fluorescent lamps for a specific period. The results indicated that some of the samples could prevent the biofilm formation on the surface of the materials while the microbial growth was unaffected on the pure silicone rubber.
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