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- Billing, Matilda, et al.
(author)
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Signaling via Smad2 and Smad3 is dispensable for adult murine hematopoietic stem cell function in vivo
- 2017
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In: Experimental Hematology. - : Elsevier BV. - 0301-472X.
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Journal article (peer-reviewed)abstract
- Transforming growth factor-β (TGFβ) is a member of a large family of polypeptide growth factors. TGFβ signals mainly through the intracellular proteins Smad2 and Smad3, which are highly similar in amino acid sequence identity. A number of studies have shown that these proteins, dependent on context, have distinct roles in the TGFβ signaling pathway. TGFβ is one of the most potent inhibitors of hematopoietic stem and progenitor cell proliferation in vitro, but its role in hematopoiesis in vivo is still being determined. To circumvent possible redundancies at the receptor level and to address specifically the role of the Smad circuitry downstream of TGFβ and activin in hematopoiesis, we studied the effect of genetically deleting both Smad2 and Smad3 in adult murine hematopoietic cells. Indeed, TGFβ signaling is impaired in vitro in primitive bone marrow (BM) cells of Smad2 and Smad3 single knockout models. However, blood parameters appear normal under steady state and in the transplantation setting. Interestingly, upon deletion of both Smad2 and Smad3 in vivo, mice quickly develop a lethal inflammatory disease, suggesting that activin/TGFβ signaling is crucial for immune cell homeostasis in the adult context. Furthermore, concurrent deletion of Smad2 and Smad3 in BM cells in immune-deficient nude mice did not result in any significant alterations of the hematopoietic system. Our findings suggest that Smad2 and Smad3 function to mediate crucial aspects of the immunoregulatory properties of TGFβ, but are dispensable for any effect that TGFβ has on primitive hematopoietic cells in vivo.
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| 2. |
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| 3. |
- Dahl, Matilda, 1978-
(author)
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Reform and rescue : International organizations and the organization of markets
- 2018
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In: Organizing and reorganizing markets. - : Oxford University Press. - 9780198815761 - 9780191853289
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Book chapter (peer-reviewed)abstract
- Organizing and Reorganizing Markets is an edited volume that brings organization theory to the study of markets. The differences between markets and organizations are often exaggerated. Both are organized. Organizing exists in addition to other processes and phenomena that form markets: the mutual adaption among sellers and buyers as described in mainstream economics and the institutions described in institutional economics and economic sociology. Market organization can be analysed with the same type of theories used for analysing organization within formal organizations. Through the use of many empirical examples, the book demonstrates how this can be done. We argue that the way a certain market is organized can be understood as the (intermediate) result of previous organizing processes. We discuss such questions as ‘What drives market organizing and reorganizing processes? What makes various organizations intervene as market organizers? And how are the specific contents of market organization determined?’ The answers to these questions help us to analyse similarities and differences among organizing processes in formal organizations and those in markets. The arguments are illustrated by in-depth studies of many types of markets. The book is intended to open up markets as a field of study for scholars of organization. Although the chapters have different authors, they use and elaborate upon the same general theoretical framework. The book contributes to the issue of organization outside and among organizations where a fundamental concept is that of partial organization.
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| 5. |
- Rörby, Emma, et al.
(author)
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The stem cell regulator PEDF is dispensable for maintenance and function of hematopoietic stem cells
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Journal article (peer-reviewed)abstract
- Pigment epithelium derived factor (PEDF), a ubiquitously expressed 50 kDa secreted glycoprotein, was recently discovered to regulate self-renewal of neural stem cells and have a supportive effect on human embryonic stem cell growth. Here, we analyzed expression of PEDF in the murine hematopoietic stem cell (HSC) compartments and found that PEDF is highly expressed in primary long-term HSCs. Therefore, we characterized the hematopoietic system in a knockout mouse model for PEDF and using this model we surprisingly found that PEDF is dispensable for HSC regulation. PEDF knockout mice exhibit normal hematopoiesis in steady state conditions and the absence of PEDF lead to normal regeneration capacity in a serial competitive transplantation setting. Additionally, PEDF-deficient cells exhibit unaltered lineage distribution upon serial transplantations. When human cord blood stem and progenitor cells were cultured in media supplemented with recombinant PEDF they did not show changes in growth potential. Taken together, we report that PEDF is not a critical regulatory factor for HSC function during regeneration in vivo or growth of human stem/progenitor cells in vitro.
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