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  1. Article ; Online: Neuroectoderm phenotypes in a human stem cell model of O-GlcNAc transferase associated with intellectual disability.

    Murray, Marta / Davidson, Lindsay / Ferenbach, Andrew T / Lefeber, Dirk / van Aalten, Daan M F

    Molecular genetics and metabolism

    2024  Volume 142, Issue 2, Page(s) 108492

    Abstract: Pathogenic variants in the O-GlcNAc transferase gene (OGT) have been associated with a congenital disorder of glycosylation (OGT-CDG), presenting with intellectual disability which may be of neuroectodermal origin. To test the hypothesis that pathology ... ...

    Abstract Pathogenic variants in the O-GlcNAc transferase gene (OGT) have been associated with a congenital disorder of glycosylation (OGT-CDG), presenting with intellectual disability which may be of neuroectodermal origin. To test the hypothesis that pathology is linked to defects in differentiation during early embryogenesis, we developed an OGT-CDG induced pluripotent stem cell line together with isogenic control generated by CRISPR/Cas9 gene-editing. Although the OGT-CDG variant leads to a significant decrease in OGT and O-GlcNAcase protein levels, there were no changes in differentiation potential or stemness. However, differentiation into ectoderm resulted in significant differences in O-GlcNAc homeostasis. Further differentiation to neuronal stem cells revealed differences in morphology between patient and control lines, accompanied by disruption of the O-GlcNAc pathway. This suggests a critical role for O-GlcNAcylation in early neuroectoderm architecture, with robust compensatory mechanisms in the earliest stages of stem cell differentiation.
    Language English
    Publishing date 2024-05-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1418518-0
    ISSN 1096-7206 ; 1096-7192
    ISSN (online) 1096-7206
    ISSN 1096-7192
    DOI 10.1016/j.ymgme.2024.108492
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  2. Article ; Online: Development of a human iPSC-derived placental barrier-on-chip model.

    Lermant, Agathe / Rabussier, Gwenaëlle / Lanz, Henriëtte L / Davidson, Lindsay / Porter, Iain M / Murdoch, Colin E

    iScience

    2023  Volume 26, Issue 7, Page(s) 107240

    Abstract: Although recently developed placenta-on-chip systems opened promising perspectives for placental barrier modeling, they still lack physiologically relevant trophoblasts and are poorly amenable to high-throughput studies. We aimed to implement human- ... ...

    Abstract Although recently developed placenta-on-chip systems opened promising perspectives for placental barrier modeling, they still lack physiologically relevant trophoblasts and are poorly amenable to high-throughput studies. We aimed to implement human-induced pluripotent stem cells (hiPSC)-derived trophoblasts into a multi-well microfluidic device to develop a physiologically relevant and scalable placental barrier model. When cultured in a perfused micro-channel against a collagen-based matrix, hiPSC-derived trophoblasts self-arranged into a 3D structure showing invasive behavior, fusogenic and endocrine activities, structural integrity, and expressing placental transporters. RNA-seq analysis revealed that the microfluidic 3D environment boosted expression of genes related to early placental structural development, mainly involved in mechanosensing and cell surface receptor signaling. These results demonstrated the feasibility of generating a differentiated primitive syncytium from hiPSC in a microfluidic platform. Besides expanding hiPSC-derived trophoblast scope of applications, this study constitutes an important resource to improve placental barrier models and boost research and therapeutics evaluation in pregnancy.
    Language English
    Publishing date 2023-07-13
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.107240
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  3. Article ; Online: Human spinal cord in vitro differentiation pace is initially maintained in heterologous embryonic environments.

    Dady, Alwyn / Davidson, Lindsay / Halley, Pamela A / Storey, Kate G

    eLife

    2022  Volume 11

    Abstract: Species-specific differentiation pace in vitro indicates that some aspects of neural differentiation are governed by cell intrinsic properties. Here we describe a novel in vitro human neural-rosette assay that recapitulates dorsal spinal cord ... ...

    Abstract Species-specific differentiation pace in vitro indicates that some aspects of neural differentiation are governed by cell intrinsic properties. Here we describe a novel in vitro human neural-rosette assay that recapitulates dorsal spinal cord differentiation but proceeds more rapidly than in the human embryo, suggesting that it lacks endogenous signalling dynamics. To test whether in vitro conditions represent an intrinsic differentiation pace, human iPSC-derived neural rosettes were challenged by grafting into the faster differentiating chicken embryonic neural tube iso-chronically, or hetero-chronically into older embryos. In both contexts in vitro differentiation pace was initially unchanged, while long-term analysis revealed iso-chronic slowed and hetero-chronic conditions promoted human neural differentiation. Moreover, hetero-chronic conditions did not alter the human neural differentiation programme, which progressed to neurogenesis, while the host embryo advanced into gliogenesis. This study demonstrates that intrinsic properties limit human differentiation pace, and that timely extrinsic signals are required for progression through an intrinsic human neural differentiation programme.
    MeSH term(s) Animals ; Cell Differentiation ; Chick Embryo ; Humans ; Induced Pluripotent Stem Cells ; Neural Tube ; Neurogenesis ; Spinal Cord
    Language English
    Publishing date 2022-02-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.67283
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  4. Article: Quantitative Proteomics of Polarised Macrophages Derived from Induced Pluripotent Stem Cells.

    Murugesan, Gavuthami / Davidson, Lindsay / Jannetti, Linda / Crocker, Paul R / Weigle, Bernd

    Biomedicines

    2022  Volume 10, Issue 2

    Abstract: Macrophages ( ... ...

    Abstract Macrophages (M
    Language English
    Publishing date 2022-01-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10020239
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  5. Article ; Online: A 3-year experience implementing blended TBL: active instructional methods can shift student attitudes to learning.

    Davidson, Lindsay K

    Medical teacher

    2011  Volume 33, Issue 9, Page(s) 750–753

    Abstract: Medical educators have been encouraged to adopt active instructional strategies that require learners to engage in and direct their own learning. These innovations may be seen as disruptive and face early challenges due to student resistance. We report 3 ...

    Abstract Medical educators have been encouraged to adopt active instructional strategies that require learners to engage in and direct their own learning. These innovations may be seen as disruptive and face early challenges due to student resistance. We report 3 years of experience implementing a blend of team-based learning (TBL) and online learning modules in an undergraduate medical course. Three sequential cohorts of first year medical students were surveyed exploring how they valued different instructional methods during a period of evolving curricular design. In addition to a demonstrated increase in acceptance of new teaching methods, there was a shift in student perceptions of the relative merits of didactic, online and TBL teaching. Medical students' appreciations of different instructional methods are influenced by the maturity of instructional design. Educational change is best viewed through a longer term lens, acknowledging the necessity for teachers to develop experience in implementing new methods in the context of their institution.
    MeSH term(s) Attitude ; Cooperative Behavior ; Data Collection ; Education, Medical, Undergraduate ; Humans ; Problem-Based Learning ; Program Development ; Program Evaluation ; Students, Medical/psychology
    Language English
    Publishing date 2011
    Publishing country England
    Document type Journal Article
    ZDB-ID 424426-6
    ISSN 1466-187X ; 0142-159X
    ISSN (online) 1466-187X
    ISSN 0142-159X
    DOI 10.3109/0142159X.2011.558948
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  6. Article ; Online: Identification of SUMO Targets Associated With the Pluripotent State in Human Stem Cells.

    Mojsa, Barbara / Tatham, Michael H / Davidson, Lindsay / Liczmanska, Magda / Branigan, Emma / Hay, Ronald T

    Molecular & cellular proteomics : MCP

    2021  Volume 20, Page(s) 100164

    Abstract: To investigate the role of SUMO modification in the maintenance of pluripotent stem cells, we used ML792, a potent and selective inhibitor of SUMO Activating Enzyme. Treatment of human induced pluripotent stem cells with ML792 resulted in the loss of key ...

    Abstract To investigate the role of SUMO modification in the maintenance of pluripotent stem cells, we used ML792, a potent and selective inhibitor of SUMO Activating Enzyme. Treatment of human induced pluripotent stem cells with ML792 resulted in the loss of key pluripotency markers. To identify putative effector proteins and establish sites of SUMO modification, cells were engineered to stably express either SUMO1 or SUMO2 with C-terminal TGG to KGG mutations that facilitate GlyGly-K peptide immunoprecipitation and identification. A total of 976 SUMO sites were identified in 427 proteins. STRING enrichment created three networks of proteins with functions in regulation of gene expression, ribosome biogenesis, and RNA splicing, although the latter two categories represented only 5% of the total GGK peptide intensity. The rest have roles in transcription and the regulation of chromatin structure. Many of the most heavily SUMOylated proteins form a network of zinc-finger transcription factors centered on TRIM28 and associated with silencing of retroviral elements. At the level of whole proteins, there was only limited evidence for SUMO paralogue-specific modification, although at the site level there appears to be a preference for SUMO2 modification over SUMO1 in acidic domains. We show that SUMO influences the pluripotent state in hiPSCs and identify many chromatin-associated proteins as bona fide SUMO substrates in human induced pluripotent stem cells.
    MeSH term(s) Cell Line ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Proteomics ; Small Ubiquitin-Related Modifier Proteins/metabolism ; Sumoylation
    Chemical Substances Small Ubiquitin-Related Modifier Proteins
    Language English
    Publishing date 2021-10-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2075924-1
    ISSN 1535-9484 ; 1535-9476
    ISSN (online) 1535-9484
    ISSN 1535-9476
    DOI 10.1016/j.mcpro.2021.100164
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  7. Article ; Online: ERK1/2 signalling dynamics promote neural differentiation by regulating chromatin accessibility and the polycomb repressive complex.

    Semprich, Claudia I / Davidson, Lindsay / Amorim Torres, Adriana / Patel, Harshil / Briscoe, James / Metzis, Vicki / Storey, Kate G

    PLoS biology

    2022  Volume 20, Issue 12, Page(s) e3000221

    Abstract: Fibroblast growth factor (FGF) is a neural inducer in many vertebrate embryos, but how it regulates chromatin organization to coordinate the activation of neural genes is unclear. Moreover, for differentiation to progress, FGF signalling must decline. ... ...

    Abstract Fibroblast growth factor (FGF) is a neural inducer in many vertebrate embryos, but how it regulates chromatin organization to coordinate the activation of neural genes is unclear. Moreover, for differentiation to progress, FGF signalling must decline. Why these signalling dynamics are required has not been determined. Here, we show that dephosphorylation of the FGF effector kinase ERK1/2 rapidly increases chromatin accessibility at neural genes in mouse embryos, and, using ATAC-seq in human embryonic stem cell derived spinal cord precursors, we demonstrate that this occurs genome-wide across neural genes. Importantly, ERK1/2 inhibition induces precocious neural gene transcription, and this involves dissociation of the polycomb repressive complex from key gene loci. This takes place independently of subsequent loss of the repressive histone mark H3K27me3 and transcriptional onset. Transient ERK1/2 inhibition is sufficient for the dissociation of the repressive complex, and this is not reversed on resumption of ERK1/2 signalling. Moreover, genomic footprinting of sites identified by ATAC-seq together with ChIP-seq for polycomb protein Ring1B revealed that ERK1/2 inhibition promotes the occupancy of neural transcription factors (TFs) at non-polycomb as well as polycomb associated sites. Together, these findings indicate that ERK1/2 signalling decline promotes global changes in chromatin accessibility and TF binding at neural genes by directing polycomb and other regulators and appears to serve as a gating mechanism that provides directionality to the process of differentiation.
    MeSH term(s) Mice ; Humans ; Animals ; Chromatin ; MAP Kinase Signaling System ; Polycomb-Group Proteins/genetics ; Polycomb-Group Proteins/metabolism ; Cell Differentiation ; Signal Transduction
    Chemical Substances Chromatin ; Polycomb-Group Proteins
    Language English
    Publishing date 2022-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3000221
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  8. Article ; Online: Shark sanctuaries: substance or spin?

    Davidson, Lindsay N K

    Science (New York, N.Y.)

    2012  Volume 338, Issue 6114, Page(s) 1538–1539

    MeSH term(s) Animals ; Conservation of Natural Resources/legislation & jurisprudence ; Fisheries ; Population Dynamics ; Sharks
    Language English
    Publishing date 2012-12-21
    Publishing country United States
    Document type Letter
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.338.6114.1538
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  9. Article ; Online: Global marine protected areas to prevent extinctions.

    Davidson, Lindsay N K / Dulvy, Nicholas K

    Nature ecology & evolution

    2017  Volume 1, Issue 2, Page(s) 40

    Abstract: One goal of global marine protected areas (MPAs) is to ensure they represent a breadth of taxonomic biodiversity. Ensuring representation of species in MPAs, however, would require protecting vast areas of the global oceans and does not explicitly ... ...

    Abstract One goal of global marine protected areas (MPAs) is to ensure they represent a breadth of taxonomic biodiversity. Ensuring representation of species in MPAs, however, would require protecting vast areas of the global oceans and does not explicitly prioritize species of conservation concern. When threatened species are considered, a recent study found that only a small fraction of their geographic ranges are within the global MPA network. Which global marine areas, and what conservation actions beyond MPAs could be prioritized to prevent marine extinctions (Convention on Biological Diversity Aichi Target 12), remains unknown. Here, we use systematic conservation planning approaches to prioritize conservation actions for sharks, rays and chimaeras (class Chondrichthyes). We use chondrichthyans as they have the highest proportion of threatened species of any marine class. We find that expanding the MPA network by 3% in 70 nations would cover half of the geographic range of 99 imperilled endemic chondrichthyans. Our hotspot analysis reveals that just 12 nations harbour more than half (53) of the imperilled endemics. Four of these hotspot nations are within the top ten chondrichthyan fishing nations in the world, but are yet to implement basic chondrichthyan fisheries management. Given their geopolitical realities, conservation action for some countries will require relief and reorganization to enable sustainable fisheries and species protection.
    Language English
    Publishing date 2017-01-23
    Publishing country England
    Document type Journal Article
    ISSN 2397-334X
    ISSN (online) 2397-334X
    DOI 10.1038/s41559-016-0040
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  10. Article: Variety show syndrome: making a diagnosis.

    Davidson, Lindsay

    Medical education

    2003  Volume 37, Issue 11, Page(s) 1034

    MeSH term(s) Education, Medical ; Education, Medical, Undergraduate/methods ; Faculty, Medical ; Humans ; Specialization ; Teaching/methods
    Language English
    Publishing date 2003-09-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 195274-2
    ISSN 1365-2923 ; 0308-0110
    ISSN (online) 1365-2923
    ISSN 0308-0110
    DOI 10.1046/j.1365-2923.2003.01659.x
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