| 1. |
- Lock, John G, et al.
(författare)
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Reticular adhesions are a distinct class of cell-matrix adhesions that mediate attachment during mitosis
- 2018
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Ingår i: Nature Cell Biology. - Stockholm : Karolinska Institutet, Dept of Biosciences and Nutrition. - 1465-7392 .- 1476-4679.
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Tidskriftsartikel (refereegranskat)abstract
- Adhesion to the extracellular matrix persists during mitosis in most cell types. However, while classical adhesion complexes, such as focal adhesions, do and must disassemble to enable mitotic rounding, the mechanisms of residual mitotic cell-extracellular matrix adhesion remain undefined. Here, we identify 'reticular adhesions', a class of adhesion complex that is mediated by integrin alpha v beta 5, formed during interphase, and preserved at cell-extracellular matrix attachment sites throughout cell division. Consistent with this role, integrin beta 5 depletion perturbs mitosis and disrupts spatial memory transmission between cell generations. Reticular adhesions are morphologically and dynamically distinct from classical focal adhesions. Mass spectrometry defines their unique composition, enriched in phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P-2)-binding proteins but lacking virtually all consensus adhesome components. Indeed, reticular adhesions are promoted by PtdIns(4,5)P-2, and form independently of talin and F-actin. The distinct characteristics of reticular adhesions provide a solution to the problem of maintaining cell-extracellular matrix attachment during mitotic rounding and division.
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| 5. |
- Costa, Guilherme, et al.
(författare)
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Asymmetric division coordinates collective cell migration in angiogenesis
- 2016
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 18:12, s. 1292-
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Tidskriftsartikel (refereegranskat)abstract
- The asymmetric division of stem or progenitor cells generates daughters with distinct fates and regulates cell diversity during tissue morphogenesis. However, roles for asymmetric division in other more dynamic morphogenetic processes, such as cell migration, have not previously been described. Here we combine zebrafish in vivo experimental and computational approaches to reveal that heterogeneity introduced by asymmetric division generates multicellular polarity that drives coordinated collective cell migration in angiogenesis. We find that asymmetric positioning of the mitotic spindle during endothelial tip cell division generates daughters of distinct size with discrete 'tip' or 'stalk' thresholds of pro-migratory Vegfr signalling. Consequently, post-mitotic Vegfr asymmetry drives Dll4/Notch-independent self-organization of daughters into leading tip or trailing stalk cells, and disruption of asymmetry randomizes daughter tip/stalk selection. Thus, asymmetric division seamlessly integrates cell proliferation with collective migration, and, as such, may facilitate growth of other collectively migrating tissues during development, regeneration and cancer invasion.
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| 6. |
- De Luca, Michele, et al.
(författare)
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Advances in stem cell research and therapeutic development
- 2019
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 21:7, s. 801-811
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Forskningsöversikt (refereegranskat)abstract
- Despite many reports of putative stem-cell-based treatments in genetic and degenerative disorders or severe injuries, the number of proven stem cell therapies has remained small. In this Review, we survey advances in stem cell research and describe the cell types that are currently being used in the clinic or are close to clinical trials. Finally, we analyse the scientific rationale, experimental approaches, caveats and results underpinning the clinical use of such stem cells.
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| 8. |
- Hosono, Chie, et al.
(författare)
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Transient junction anisotropies orient annular cell polarization in the Drosophila airway tubes
- 2015
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 17:12, s. 1569-1576
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to planes, three-dimensional (3D) structures such as tubes are physically anisotropic. Tubular organs exhibit a striking orientation of landmarks according to the physical anisotropy of the 3D shape(1-4), in addition to planar cell polarization(5,6). However, the influence of 3D tissue topography on the constituting cells remains underexplored(7-9). Here, we identify a regulatory network polarizing cellular biochemistry according to the physical anisotropy of the 3D tube geometry (tube cell polarization) by a genome-wide, tissue-specific RNAi screen. During Drosophila airway remodelling, each apical cellular junction is equipotent to establish perpendicular actomyosin cables, irrespective of the longitudinal or transverse tube axis. A dynamic transverse enrichment of atypical protein kinase C (aPKC) shifts the balance and transiently targets activated small GTPase RhoA, myosin phosphorylation and Rab11 vesicle trafficking to longitudinal junctions. We propose that the PAR complex translates tube physical anisotropy into longitudinal junctional anisotropy, where cell cell communication aligns the contractile cytoskeleton of neighbouring cells.
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| 10. |
- Jiang, Dongsheng, et al.
(författare)
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Two succeeding fibroblastic lineages drive dermal development and the transition from regeneration to scarring
- 2018
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Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 20:4, s. 422-431
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Tidskriftsartikel (refereegranskat)abstract
- During fetal development, mammalian back-skin undergoes a natural transition in response to injury, from scarless regeneration to skin scarring. Here, we characterize dermal morphogenesis and follow two distinct embryonic fibroblast lineages, based on their history of expression of the engrailed 1 gene. We use single-cell fate-mapping, live three dimensional confocal imaging and in silico analysis coupled with immunolabelling to reveal unanticipated structural and regional complexity and dynamics within the dermis. We show that dermal development and regeneration are driven by engrailed 1-history-naive fibroblasts, whose numbers subsequently decline. Conversely, engrailed 1-history-positive fibroblasts possess scarring abilities at this early stage and their expansion later on drives scar emergence. The transition can be reversed, locally, by transplanting engrailed 1-naive cells. Thus, fibroblastic lineage replacement couples the decline of regeneration with the emergence of scarring and creates potential clinical avenues to reduce scarring.
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