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| 2. |
- Adolfsson, Jörgen, et al.
(författare)
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Identification of Flt3(+) lympho-myeloid stem cells lacking erythro-megakaryocytic potential: A revised road map for adult blood lineage commitment
- 2005
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Ingår i: Cell. - : Elsevier (Cell Press). - 0092-8674 .- 1097-4172. ; 121:2, s. 295-306
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Tidskriftsartikel (refereegranskat)abstract
- All blood cell lineages derive from a common hematopoietic stem cell (HSC). The current model implicates that the first lineage commitment step of adult pluripotent HSCs results in a strict separation into common lymphoid and common myeloid precursors. We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell potentials but in contrast to Lin-Sca-1(+)ckit(+)Flt3(-) HSCs fail to produce significant erythroid and megakaryocytic progeny. This distinct lineage restriction site is accompanied by downregulation of genes for regulators of erythroid and megakaryocyte development. In agreement with representing a lymphoid primed progenitor, Lin(-)Sca-l(+)c-kit(+)CD34(+)Flt3(+) cells display upregulated IL-7 receptor gene expression. Based on these observations, we propose a revised road map for adult blood lineage development.
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| 3. |
- Baumgardt, Magnus, 1976-, et al.
(författare)
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Neuronal Subtype Specification within a Lineage by Opposing Temporal Feed-Forward Loops
- 2009
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Ingår i: Cell. - Cambridge,MA, USA : Cell Press. - 0092-8674 .- 1097-4172. ; 139:5, s. 969-982
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Tidskriftsartikel (refereegranskat)abstract
- Neural progenitors generate distinct cell types at different stages, but the mechanisms controlling these temporal transitions are poorly understood. In the Drosophila CNS, a cascade of transcription factors, the ‘temporal gene cascade’, has been identified, that acts to alter progenitor competence over time. However, many CNS lineages display broad temporal windows, and it is unclear how broad windows progress into sub-windows that generate unique cell types. We have addressed this issue in an identifiable Drosophila CNS lineage, and find that a broad castor temporal window is sub-divided by two different feed-forward loops, both of which are triggered by castor itself. The first loop acts to specify a unique cell fate, while the second loop suppresses the first loop, thereby allowing for the generation of alternate cell fates. This mechanism of temporal and ‘sub-temporal’ genes acting in opposing feed-forward loops may be used by many stem cell lineages to generate diversity.
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| 7. |
- Chang, Lufen, et al.
(författare)
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The E3 ubiquitin ligase itch couples JNK activation to TNFα-induced cell death by inducing c-FLIP L turnover
- 2006
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Ingår i: Cell. - 0092-8674 .- 1097-4172. ; 124:3, s. 601-613
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Tidskriftsartikel (refereegranskat)abstract
- The proinflammatory cytokine tumor necrosis factor (TNF) α signals both cell survival and death. The biological outcome of TNFα treatment is determined by the balance between NF-κB and Jun kinase (JNK) signaling; NF-κB promotes survival, whereas JNK enhances cell death. Critically, identity of a JNK substrate that promotes TNFα-induced apoptosis has been outstanding. Here we show that TNFα-mediated JNK activation accelerates turnover of the NF-κB-induced antiapoptotic protein c-FLIP, an inhibitor of caspase-8. This is not due to direct c-FLIP phosphorylation but depends on JNK-mediated phosphorylation and activation of the E3 ubiquitin ligase Itch, which specifically ubiquitinates c-FLIP and induces its proteasomal degradation. JNK1 or Itch deficiency or treatment with a JNK inhibitor renders mice resistant in three distinct models of TNFα-induced acute liver failure, and cells from these mice do not display inducible c-FLIPL ubiquitination and degradation. Thus, JNK antagonizes NF-κB during TNFα signaling by promoting the proteasomal elimination of c-FLIPL.
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| 10. |
- Falkenberg, Maria, 1968, et al.
(författare)
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Structure casts light on mtDNA replication.
- 2009
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 139:2, s. 231-3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this issue, Lee et al. (2009) present a crystal structure of the human mitochondrial DNA polymerase (POLgamma). The structure of this heterotrimeric enzyme lays a foundation for understanding how POLgamma mutations cause human mitochondrial disease and why some antiviral nucleoside analogs cause cellular toxicity.
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