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- Merino Martinez, R, et al.
(författare)
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Human exposome assessment platform
- 2021
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Ingår i: Environmental epidemiology (Philadelphia, Pa.). - 2474-7882. ; 5:6, s. e182-
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Holmberg, J, et al.
(författare)
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SoxB1 transcription factors and Notch signaling use distinct mechanisms to regulate proneural gene function and neural progenitor differentiation
- 2008
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 135:10, s. 1843-1851
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Tidskriftsartikel (refereegranskat)abstract
- The preservation of a pool of neural precursors is a prerequisite for proper establishment and maintenance of a functional central nervous system(CNS). Both Notch signaling and SoxB1 transcription factors have been ascribed key roles during this process, but whether these factors use common or distinct mechanisms to control progenitor maintenance is unsettled. Here, we report that the capacity of Notch to maintain neural cells in an undifferentiated state requires the activity of SoxB1 proteins, whereas the mechanism by which SoxB1 block neurogenesis is independent of Notch signaling. A common feature of Notch signaling and SoxB1 proteins is their ability to inhibit the activity of proneural bHLH proteins. Notch represses the transcription of proneural bHLH genes, while SoxB1 proteins block their neurogenic capacity. Moreover, E-proteins act as functional partners of proneural proteins and the suppression of E-protein expression is an important mechanism by which Notch counteracts neurogenesis. Interestingly, in contrast to the Hes-dependent repression of proneural genes, suppression of E-protein occurs in a Hes-independent fashion. Together, these data reveal that Notch signaling and SoxB1 transcription factors use distinct regulatory mechanisms to control proneural protein function and to preserve neural cells as undifferentiated precursors.
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| 8. |
- Marklund, U, et al.
(författare)
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Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression
- 2010
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 137:3, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- Homeodomain (HD) transcription factors and components of the Notch pathway [Delta1 (Dll1), Jagged1 (Jag1) and the Fringe (Fng) proteins] are expressed in distinct progenitor domains along the dorsoventral (DV) axis of the developing spinal cord. However, the internal relationship between these two regulatory pathways has not been established. In this report we show that HD proteins act upstream of Notch signalling. Thus, HD proteins control the spatial distribution of Notch ligands and Fng proteins, whereas perturbation of the Notch pathway does not affect the regional expression of HD proteins. Loss of Dll1 or Jag1 leads to a domain-specific increase of neuronal differentiation but does not affect the establishment of progenitor domain boundaries. Moreover, gain-of-function experiments indicate that the ability of Dll1 and Jag1 to activate Notch is limited to progenitors endogenously expressing the respective ligand. Fng proteins enhance Dll1-activated Notch signalling and block Notch activation mediated by Jag1. This finding, combined with the overlapping expression of Fng with Dll1 but not with Jag1, is likely to explain the domain-specific activity of the Notch ligands. This outcome is opposite to the local regulation of Notch activity in most other systems, including the Drosophila wing, where Fng co-localizes with Jagged/Serrate rather than Dll/Delta, which facilitates Notch signalling at regional boundaries instead of within domains. The regulation of Notch activation in the spinal cord therefore appears to endow specific progenitor populations with a domain-wide autonomy in the control of neurogenesis and prevents any inadequate activation of Notch across progenitor domain boundaries.
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- Riechers, Maraja, et al.
(författare)
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Key advantages of the leverage points perspective to shape human-nature relations
- 2021
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Ingår i: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 17:1, s. 205-214
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Tidskriftsartikel (refereegranskat)abstract
- This perspective paper synthesises the special issue 'Human-nature connectedness as a leverage point for sustainability transformation'. Based on the articles in this special issue, we aim to foster the operationalisation of the leverage points perspective to shape human-nature relations to enable sustainability transformations. Specifically, we draw on four key advantages of the leverage points perspective: (i) the explicit recognition of deep leverage points; (ii) the ability to examine the interactions between shallow and deep system changes; (iii) the combination of causal and teleological modes of research; and (iv) the ability to function as a methodological boundary object. The contributions to this special issue revealed three deep leverage points addressing paradigm shifts in research and beyond: relational thinking and values, stewardship philosophy and shifting the economic growth paradigm to focus on human well-being. We highlight interlinkages between leverage points to further strengthen the transformative potential of interventions that aim at triggering shifts in our understanding about human-nature relations. Further, we show a way to bridge causal and teleological approaches by envisioning desired futures. Lastly, we emphasise the potential of arts-based methodologies, including participatory, transdisciplinary research to foster sustainability transformation and how this can be combined within the leverage points perspective.
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- Bergsland, M, et al.
(författare)
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Sequentially acting Sox transcription factors in neural lineage development
- 2011
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Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 25:23, s. 2453-2464
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Tidskriftsartikel (refereegranskat)abstract
- Pluripotent embryonic stem (ES) cells can generate all cell types, but how cell lineages are initially specified and maintained during development remains largely unknown. Different classes of Sox transcription factors are expressed during neurogenesis and have been assigned important roles from early lineage specification to neuronal differentiation. Here we characterize the genome-wide binding for Sox2, Sox3, and Sox11, which have vital functions in ES cells, neural precursor cells (NPCs), and maturing neurons, respectively. The data demonstrate that Sox factor binding depends on developmental stage-specific constraints and reveal a remarkable sequential binding of Sox proteins to a common set of neural genes. Interestingly, in ES cells, Sox2 preselects for neural lineage-specific genes destined to be bound and activated by Sox3 in NPCs. In NPCs, Sox3 binds genes that are later bound and activated by Sox11 in differentiating neurons. Genes prebound by Sox proteins are associated with a bivalent chromatin signature, which is resolved into a permissive monovalent state upon binding of activating Sox factors. These data indicate that a single key transcription factor family acts sequentially to coordinate neural gene expression from the early lineage specification in pluripotent cells to later stages of neuronal development.
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| 21. |
- Bergsland, M, et al.
(författare)
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The establishment of neuronal properties is controlled by Sox4 and Sox11
- 2006
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Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 20:24, s. 3475-3486
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Tidskriftsartikel (refereegranskat)abstract
- The progression of neurogenesis relies on proneural basic helix–loop–helix (bHLH) transcription factors. These factors operate in undifferentiated neural stem cells and induce cell cycle exit and the initiation of a neurogenic program. However, the transient expression of proneural bHLH proteins in neural progenitors indicates that expression of neuronal traits must rely on previously unexplored mechanisms operating downstream from proneural bHLH proteins. Here we show that the HMG-box transcription factors Sox4 and Sox11 are of critical importance, downstream from proneural bHLH proteins, for the establishment of pan-neuronal protein expression. Examination of a neuronal gene promoter reveals that Sox4 and Sox11 exert their functions as transcriptional activators. Interestingly, the capacity of Sox4 and Sox11 to induce the expression of neuronal traits is independent of mechanisms regulating the exit of neural progenitors from the cell cycle. The transcriptional repressor protein REST/NRSF has been demonstrated to block neuronal gene expression in undifferentiated neural cells. We now show that REST/NRSF restricts the expression of Sox4 and Sox11, explaining how REST/NRSF can prevent precocious expression of neuronal proteins. Together, these findings demonstrate a central regulatory role of Sox4 and Sox11 during neuronal maturation and mechanistically separate cell cycle withdrawal from the establishment of neuronal properties.
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| 25. |
- Hagey, DW, et al.
(författare)
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CYCLIN-B1/2 and -D1 act in opposition to coordinate cortical progenitor self-renewal and lineage commitment
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 2898-
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Tidskriftsartikel (refereegranskat)abstract
- The sequential generation of layer-specific cortical neurons requires radial glia cells (RGCs) to precisely balance self-renewal and lineage commitment. While specific cell-cycle phases have been associated with these decisions, the mechanisms linking the cell-cycle machinery to cell-fate commitment remain obscure. Using single-cell RNA-sequencing, we find that the strongest transcriptional signature defining multipotent RGCs is that of G2/M-phase, and particularly CYCLIN-B1/2, while lineage-committed progenitors are enriched in G1/S-phase genes, including CYCLIN-D1. These data also reveal cell-surface markers that allow us to isolate RGCs and lineage-committed progenitors, and functionally confirm the relationship between cell-cycle phase enrichment and cell fate competence. Finally, we use cortical electroporation to demonstrate that CYCLIN-B1/2 cooperate with CDK1 to maintain uncommitted RGCs by activating the NOTCH pathway, and that CYCLIN-D1 promotes differentiation. Thus, this work establishes that cell-cycle phase-specific regulators act in opposition to coordinate the self-renewal and lineage commitment of RGCs via core stem cell regulatory pathways.
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