| 1. |
- Balboa, Diego, et al.
(författare)
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Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.
- 2022
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 40:7, s. 1042-1055
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in the generation of stem-cell-derived islets (SC-islets), no detailed characterization of their functional properties has been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and benchmarked them comprehensively against primary adult islets. Biphasic glucose-stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and the increasing presence of alpha cells. Electrophysiology, signaling and exocytosis of SC-islets were similar to those of adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of engraftment in mice revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.
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| 2. |
- De Wit, Pierre, 1978, et al.
(författare)
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Genetic Variation in Swedish Marine Clitellates
- 2008
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Ingår i: Poster presented at Systematikdagarna 2008, Uppsala, Sweden 24-25 November 2008.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Erséus, Christer, 1951, et al.
(författare)
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Barcoding worms
- 2007
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Ingår i: JMBA Global Marine Environment. ; 2007:6
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
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| 5. |
- Ibrahim, Hazem, et al.
(författare)
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RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function
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Ingår i: Diabetologia. - 0012-186X.
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Regulatory factor X 6 (RFX6) is crucial for pancreatic endocrine development and differentiation. The RFX6 variant p.His293LeufsTer7 is significantly enriched in the Finnish population, with almost 1:250 individuals as a carrier. Importantly, the FinnGen study indicates a high predisposition for heterozygous carriers to develop type 2 and gestational diabetes. However, the precise mechanism of this predisposition remains unknown. Methods: To understand the role of this variant in beta cell development and function, we used CRISPR technology to generate allelic series of pluripotent stem cells. We created two isogenic stem cell models: a human embryonic stem cell model; and a patient-derived stem cell model. Both were differentiated into pancreatic islet lineages (stem-cell-derived islets, SC-islets), followed by implantation in immunocompromised NOD-SCID-Gamma mice. Results: Stem cell models of the homozygous variant RFX6−/− predictably failed to generate insulin-secreting pancreatic beta cells, mirroring the phenotype observed in Mitchell–Riley syndrome. Notably, at the pancreatic endocrine stage, there was an upregulation of precursor markers NEUROG3 and SOX9, accompanied by increased apoptosis. Intriguingly, heterozygous RFX6+/− SC-islets exhibited RFX6 haploinsufficiency (54.2% reduction in protein expression), associated with reduced beta cell maturation markers, altered calcium signalling and impaired insulin secretion (62% and 54% reduction in basal and high glucose conditions, respectively). However, RFX6 haploinsufficiency did not have an impact on beta cell number or insulin content. The reduced insulin secretion persisted after in vivo implantation in mice, aligning with the increased risk of variant carriers to develop diabetes. Conclusions/interpretation: Our allelic series isogenic SC-islet models represent a powerful tool to elucidate specific aetiologies of diabetes in humans, enabling the sensitive detection of aberrations in both beta cell development and function. We highlight the critical role of RFX6 in augmenting and maintaining the pancreatic progenitor pool, with an endocrine roadblock and increased cell death upon its loss. We demonstrate that RFX6 haploinsufficiency does not affect beta cell number or insulin content but does impair function, predisposing heterozygous carriers of loss-of-function variants to diabetes. Data availability: Ultra-deep bulk RNA-seq data for pancreatic differentiation stages 3, 5 and 7 of H1 RFX6 genotypes are deposited in the Gene Expression Omnibus database with accession code GSE234289. Original western blot images are deposited at Mendeley (https://data.mendeley.com/datasets/g75drr3mgw/2). Graphical Abstract: (Figure presented.).
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| 6. |
- Johnson, Kirk R., et al.
(författare)
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A global approach for natural history museum collections
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 379:6638, s. 1192-1194
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Tidskriftsartikel (refereegranskat)abstract
- Integration of the world’s natural history collections can provide a resource for decision-makers
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| 7. |
- Kvist, Sebastian, et al.
(författare)
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Barcoding, types and the Hirudo files: Using information content to critically evaluate the identity of DNA barcodes
- 2010
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Ingår i: Mitochondrial DNA. - 1940-1736. ; 21:6, s. 198-205
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Tidskriftsartikel (refereegranskat)abstract
- Species identifications based on DNA barcoding rely on the correct identity of previously barcoded specimens, but little attention has been given to whether deposited barcodes include correspondence to the species’ name-bearing type. The information content associated with COX1 sequences in the two most commonly used repositories of barcodes, GenBank and the Barcode of Life Data System (BOLD), is often insufficient for subsequent evaluation of the robustness of the identification procedure. We argue that DNA barcoding and taxonomy alike will benefit from more information content in the annotations of barcoded specimens as this will allow for validation and re-evaluation of the initial specimen identification. The aim should be to closely connect specimens from which reference barcodes are generated with the holotype through straight-forward taxonomy, and geographical and genetic correlations. Annotated information should also include voucher specimens and collector/identifier information.We examine two case studies based on empirical data, in which barcoding and taxonomy benefit from increased information content. On the basis of data from the first case study, we designate a barcoded neotype of the European medicinal leech, Hirudo medicinalis, on morphological and geographical grounds.
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| 8. |
- Kvist, Sebastian, et al.
(författare)
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Genetic variation and phylogeny of the cosmopolitan marine genus Tubificoides (Annelida: Clitellata: Naididae: Tubificinae).
- 2010
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Ingår i: Molecular Phylogenetics and Evolution. - 1055-7903. ; 57:2, s. 687-702
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Tidskriftsartikel (refereegranskat)abstract
- Prior attempts to resolve the phylogenetic relationships of the cosmopolitan, marine clitellate genus Tubificoides, using only morphology, resulted in unresolved trees. In this study, three mitochondrial and three nuclear loci (5912 aligned sites) were analyzed, representing 14 morphologically separate species. Genetic distances within and between these forms on the basis of the mitochondrial genes (COI, 16S and 12S) revealed that 18 distinct mitochondrial lineages were represented in the data set. After analyzing also nuclear data (28S, 18S and ITS) we conclude that 17 separately evolving lineages (i.e., phylogenetic species) were represented, including three new, cryptic species closely related to T. pseudogaster, T. amplivasatus and T. insularis, respectively. Special emphasis was put on the DNA barcoding gene (COI), which was subject to haplotype diversity analysis and, for four species, diagnostic position (as determined by the Characteristic Attribute Organization System [CAOS]) screening. Typically, the intralineage variation was 1–2 orders of magnitude smaller than the interlineage divergence, making COI useful for identification of species within Tubificoides. The genetic data corroborate that many of the morphospecies are coherent but widely distributed metapopulations. Monophyly of the genus is supported and the evolutionary history of parts of the genus is revealed by phylogenetic analysis of the combined data set. A northern hemisphere origin of the genus is suggested, and most of the widely distributed species are members of one particular clade. Two morphological characters previously emphasized in Tubificoides taxonomy (hair chaetae and cuticular papillation) were optimized on the phylogenetic tree, revealing considerable homoplasy, belying the utility of these features as phylogenetic markers.
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| 9. |
- Kvist, Sebastian, et al.
(författare)
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Two new species of Tubificoides (Annelida: Clitellata: Naididae) from the Blake Ridge methane seep in the northwest Atlantic Ocean
- 2008
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Ingår i: Proceedings of the Biological Society of Washington. - : The Biological Society of Washington. - 0006-324X. ; 121:4, s. 531-540
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Tidskriftsartikel (refereegranskat)abstract
- Tubificoides blakei and T. methanicus, both new species of oligochaetes, are described from 2156 and 2170 m depth on the Blake Ridge Diapir, near the intersection of the Carolina Rise and the Blake Ridge, off the continental shelf of North and South Carolina (U.S.A. East Coast). Tubificoides blakei is characterized by the long, parallel teeth of its bifid crotchets, and its mushroom-shaped, cuticular penis sheaths. It appears most closely related to two other deep-water species reported from the northwest Atlantic Ocean, T. bruneli Erséus, 1989 and T. aculeatus (Cook, 1969) but differs from these in the detailed morphology of the penis sheaths. Tubificoides methanicus lacks hair chaetae but is recognized by its numerous bifid chaetae, which have long, somewhat diverging teeth, the upper teeth often being longer than the lower ones, and its smooth, funnel-shaped penis sheaths. It does not seem to be closely related to any other known deep-sea species of Tubificoides, but it resembles the littoral, holarctic, T. pseudogaster (Dahl, 1960), differing from the latter mainly by its greater number and larger size of the posterior chaetae.
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| 10. |
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| 11. |
- Sundberg, Per, 1950, et al.
(författare)
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Evaluating the Utility of Single-Locus DNA Barcoding for the Identification of Ribbon Worms (Phylum Nemertea)
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Whereas many nemerteans (ribbon worms; phylum Nemertea) can be identified from external characters if observed alive, many are still problematic. When it comes to preserved specimens (as in e. g. marine inventories), there is a particular need for specimen identifier alternatives. Here, we evaluate the utility of COI (cytochrome c oxidase subunit I) as a single- locus barcoding gene. We sequenced, data mined, and compared gene fragments of COI for 915 individuals representing 161 unique taxonomic labels for 71 genera, and subjected different constellations of these to both distance-based and character-based DNA barcoding approaches, as well as species delimitation analyses. We searched for the presence or absence of a barcoding gap at different taxonomic levels (phylum, subclass, family and genus) in an attempt to understand at what level a putative barcoding gap presents itself. This was performed both using the taxonomic labels as species predictors and using objectively inferred species boundaries recovered from our species delimitation analyses. Our data suggest that COI works as a species identifier for most groups within the phylum, but also that COI data are obscured by misidentifications in sequence databases. Further, our results suggest that the number of predicted species within the dataset is (in some cases substantially) higher than the number of unique taxonomic labels-this highlights the presence of several cryptic lineages within well-established taxa and underscores the urgency of an updated taxonomic backbone for the phylum.
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| 12. |
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