Coen Campsteijn

• Timmer, Romy; Bellanger, Aurélie Nathalie Pascale; Peeters, Sarah; Kim, Hera; Ballina, Laura Rodriguez de la & Eikvar, Sissel [Show all 11 contributors for this article] (2025). LRRC59 cooperates with nuclear transporters to restrain the nuclear envelope repair machinery and safeguard genome integrity. Nature Communications. 16(1). doi: 10.1038/s41467-025-65994-4. Full text in Research Archive Show summary

  Nuclear envelope (NE) rupture is a hallmark of cancer cells, and persistent NE damage drives genome instability and inflammation. NE repair relies on activation of the endosomal sorting complex required for transport (ESCRT)-III repair machinery by the LEMD2-CHMP7 compartmentalization sensor, but little is known beyond these core factors. Here, we use convergent proximity proteomics to inventorise proteins mobilized to the NE upon assembly of LEMD2-CHMP7 and activation of ESCRT-III. Within this NE repairome, we identify LRRC59 as a critical regulator of LEMD2 accumulation at NE ruptures. We find that LRRC59, together with the nuclear transporters KPNB1 and XPO1, restricts the assembly of LEMD2-CHMP7 complexes to the site of rupture. Disruption of this regulatory axis escalates LEMD2-CHMP7 spreading across the NE, driving torsional DNA damage in ruptured nuclei and micronuclei. Thus, our work identifies a central regulatory layer of NE repair centered on LRRC59 and KPNB1. We propose that altered LRRC59 levels and deregulated nuclear transport coordinately compromise NE repair, driving genome instability and cancer development.

• Dziadkowiec, Joanna; Linga, Gaute; Kalchgruber, Lukas; Kavunga, Sunil; Cheng, Hsiu-Wei & Nilsen, Ola [Show all 9 contributors for this article] (2024). Electrochemically Assisted Growth of Hopper and Tabular Calcite under Confinement. Crystal Growth & Design. ISSN 1528-7483. 24, p. 4930–4943. doi: 10.1021/acs.cgd.3c01433. Full text in Research Archive Show summary

  Crystallization under confinement is commonplace in nature and offers new pathways to engineer crystals with the desired morphologies in a controlled and reproducible manner. In this work, we demonstrate the electrochemically assisted, in situ formation of hopper and tabular calcite crystals within a wedge-like pore formed by confinement induced by the surface force apparatus (SFA). In this geometry, the distance between the confining surfaces decreases continuously from hundreds of micrometers to a few nanometers in a single experimental setup. Calcium carbonate precipitation followed in real-time is triggered by elevating the pH and thus supersaturation directly inside the pore. The pH increase is tracked with a fluorophore tracer and calculated analytically. The unusual calcite crystal habits are obtained in the absence of precipitation-modifying additives and vary as a function of the distance between the confining walls, where at the largest surface separations, hopper crystals form on the gold surface, whereas flat, tabular calcite forms on mica when the confining distance was below 5 μm. Hexagonal or triangular calcite plates exhibit surfaces dominantly defined by rough (001) planes and increase in their surface area-to-volume ratios with decreasing SFA pore thickness. Stabilization of calcite plates bound by (001) faces is a cooperative effect of the oriented growth of calcite on the confining, negatively charged mica walls and the confinement shape, which promotes the development of calcite morphology in the rapid crystal growth directions. The heterogeneous crystallization of calcite is preceded by the nucleation and spreading of a front composed of submicrometer-sized calcium carbonate particles visualized in situ in the SFA pore. Our work demonstrates abundant crystal growth under nanoscale confinement facilitated by elevated pH and a high surface charge of the confining walls.

• Beuckeleer, Sarah De; Vanhooydonck, Andres; Daele, Johanna Van Den; Looverbosch, Tim Van De; Asselbergh, Bob & Kim, Hera [Show all 10 contributors for this article] (2024). An agarose fluidic chip for high-throughput in toto organoid imaging. Lab on a Chip. ISSN 1473-0197. 25(2), p. 235–252. doi: 10.1039/d4lc00459k. Full text in Research Archive Show summary

  Modern cell and developmental biology increasingly relies on 3D cell culture systems such as organoids. However, routine interrogation with microscopy is often hindered by tedious, non-standardized sample mounting, limiting throughput. To address these bottlenecks, we have developed a pipeline for imaging intact organoids in flow, utilizing a transparent agarose fluidic chip that enables efficient and consistent recordings with theoretically unlimited throughput. The chip, cast from a custom-designed 3D-printed mold, is coupled to a mechanically controlled syringe pump for fast and precise sample positioning. We benchmarked this setup on a commercial digitally scanned light sheet microscope with cleared glioblastoma spheroids. Spheroids of varying sizes were positioned in the field of view with micrometer-level stability, achieving a throughput of 40 one-minute recordings per hour. We further showed that sample positioning could be automated through online feedback microscopy. The optical quality of the agarose chip outperformed FEP tubing, glass channels and PDMS casts for the clearing agents used, as demonstrated by image contrast profiles of spheroids stained with a fluorescent nuclear counterstain and further emphasized by the resolution of fine microglial ramifications within cerebral organoids. The retention of image quality throughout 500 μm-sized spheroids enabled comprehensive spatial mapping of live and dead cells based on their nuclear morphology. Finally, imaging a batch of LMNA knockout vs. wildtype astrocytoma spheroids revealed significant differences in their DNA damage response, underscoring the system's sensitivity and throughput. Overall, the fluidic chip design provides a cost-effective, accessible, and efficient solution for high-throughput organoid imaging.

• Stonyte, Vilte; Mastrangelopoulou, Maria; Timmer, Romy; Lindbergsengen, Lilian; Vietri, Marina & Campsteijn, Coen [Show all 7 contributors for this article] (2023). The GCN2/eIF2αK stress kinase regulates PP1 to ensure mitotic fidelity. EMBO Reports. ISSN 1469-221X. 24(8). doi: 10.15252/embr.202256100. Full text in Research Archive Show summary

  Abstract GCN2/eIF2αK4 is exclusively seen as an eIF2α kinase, which regulates reprogramming of protein translation in response to stress. Here, we show that GCN2 has an unexpected role in unstressed cells as a regulator of mitosis. This function is not through its canonical role in translation reprogramming, but through the regulation of two previously unidentified substrates, PP1α and γ. In the absence of GCN2 function, timing and levels of phosphorylation of key mitotic players are altered, leading to aberrant chromosome alignment, missegregating chromosomes, elevated number of tripolar spindles, and a delay in progression through mitosis. Pharmacological inhibition of GCN2 results in similar effects and is synergistic with Aurora A inhibition in causing more severe mitotic errors and cell death. We suggest that GCN2‐dependent phosphorylation of PP1α and γ restrains their activity and this is important to ensure the timely regulation of phosphorylation of several PP1 substrates during early mitosis. These findings highlight a druggable PP1 inhibitor and open new avenues of research on the therapeutic potential of GCN2 inhibitors.

• Nähse, Viola; Tan, Kia Wee; Campsteijn, Coen; Brech, Andreas; Schink, Kay Oliver & Stenmark, Harald (2021). JIP4 is recruited by the phosphoinositide-binding protein Phafin2 to promote recycling tubules on macropinosomes. Journal of Cell Science. ISSN 0021-9533. 134(14), p. 1–15. doi: 10.1242/jcs.258495. Full text in Research Archive Show summary

  ABSTRACT Macropinocytosis allows cells to take up extracellular material in a non-selective manner into large vesicles called macropinosomes. After internalization, macropinosomes acquire phosphatidylinositol 3-phosphate (PtdIns3P) on their limiting membrane as they mature into endosomal-like vesicles. The molecular mechanisms that underlie recycling of membranes and transmembrane proteins from these macropinosomes still need to be defined. Here, we report that JIP4 (officially known as SPAG9), a protein previously described to bind to microtubule motors, is recruited to tubulating subdomains on macropinosomes by the PtdIns3P-binding protein Phafin2 (officially known as PLEKHF2). These JIP4-positive tubulating subdomains on macropinosomes contain F-actin, the retromer recycling complex and the retromer cargo VAMP3. Disruption of the JIP4–Phafin2 interaction, deletion of Phafin2 or inhibition of PtdIns3P production by VPS34 impairs JIP4 recruitment to macropinosomes. Whereas knockout of JIP4 suppresses tubulation, its overexpression enhances tubulation from macropinosomes. JIP4-knockout cells display increased retention of macropinocytic cargo in both early and late macropinosomes. Collectively, these data identify JIP4 and Phafin2 as components of a tubular recycling pathway that operates from macropinosomes. This article has an associated First Person interview with the first author of the paper.

• Schink, Kay Oliver; Tan, Kia Wee; Spangenberg, Helene; Martorana, Domenica; Sneeggen, Marte & Stévenin, Virginie [Show all 10 contributors for this article] (2021). The phosphoinositide coincidence detector Phafin2 promotes macropinocytosis by coordinating actin organisation at forming macropinosomes. Nature Communications. 12(1), p. 1–17. doi: 10.1038/s41467-021-26775-x. Full text in Research Archive Show summary

  Abstract Uptake of large volumes of extracellular fluid by actin-dependent macropinocytosis has an important role in infection, immunity and cancer development. A key question is how actin assembly and disassembly are coordinated around macropinosomes to allow them to form and subsequently pass through the dense actin network underlying the plasma membrane to move towards the cell center for maturation. Here we show that the PH and FYVE domain protein Phafin2 is recruited transiently to newly-formed macropinosomes by a mechanism that involves coincidence detection of PtdIns3P and PtdIns4P. Phafin2 also interacts with actin via its PH domain, and recruitment of Phafin2 coincides with actin reorganization around nascent macropinosomes. Moreover, forced relocalization of Phafin2 to the plasma membrane causes rearrangement of the subcortical actin cytoskeleton. Depletion of Phafin2 inhibits macropinosome internalization and maturation and prevents KRAS-transformed cancer cells from utilizing extracellular protein as an amino acid source. We conclude that Phafin2 promotes macropinocytosis by controlling timely delamination of actin from nascent macropinosomes for their navigation through the dense subcortical actin network.

• Vietri, Marina; Schultz, Sebastian; Bellanger, Aurélie Nathalie Pascale; Jones, Carl; Petersen, Louise I & Raiborg, Camilla [Show all 20 contributors for this article] (2020). Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmention. Nature Cell Biology. ISSN 1465-7392. 22, p. 856–867. doi: 10.1038/s41556-020-0537-5. Full text in Research Archive Show summary

  The ESCRT-III membrane fission machinery maintains the integrity of the nuclear envelope. Although primary nuclei resealing takes minutes, micronuclear envelope ruptures seem to be irreversible. Instead, micronuclear ruptures result in catastrophic membrane collapse and are associated with chromosome fragmentation and chromothripsis, complex chromosome rearrangements thought to be a major driving force in cancer development. Here we use a combination of live microscopy and electron tomography, as well as computer simulations, to uncover the mechanism underlying micronuclear collapse. We show that, due to their small size, micronuclei inherently lack the capacity of primary nuclei to restrict the accumulation of CHMP7–LEMD2, a compartmentalization sensor that detects loss of nuclear integrity. This causes unrestrained ESCRT-III accumulation, which drives extensive membrane deformation, DNA damage and chromosome fragmentation. Thus, the nuclear-integrity surveillance machinery is a double-edged sword, as its sensitivity ensures rapid repair at primary nuclei while causing unrestrained activity at ruptured micronuclei, with catastrophic consequences for genome stability.

• Landsverk, Helga Bjarnason; Sandquist, Lise Ellefsen; Bay, Lilli Theres Eilertsen; Steurer, Barbara; Campsteijn, Coen & Landsverk, Ole J. B. [Show all 10 contributors for this article] (2020). WDR82/PNUTS-PP1 Prevents Transcription-Replication Conflicts by Promoting RNA Polymerase II Degradation on Chromatin. Cell reports. 33(9). doi: 10.1016/j.celrep.2020.108469. Full text in Research Archive Show summary

  Transcription-replication (T-R) conflicts cause replication stress and loss of genome integrity. However, the transcription-related processes that restrain such conflicts are poorly understood. Here, we demonstrate that the RNA polymerase II (RNAPII) C-terminal domain (CTD) phosphatase protein phosphatase 1 (PP1) nuclear targeting subunit (PNUTS)-PP1 inhibits replication stress. Depletion of PNUTS causes lower EdU uptake, S phase accumulation, and slower replication fork rates. In addition, the PNUTS binding partner WDR82 also promotes RNAPII-CTD dephosphorylation and suppresses replication stress. RNAPII has a longer residence time on chromatin after depletion of PNUTS or WDR82. Furthermore, the RNAPII residence time is greatly enhanced by proteasome inhibition in control cells but less so in PNUTS- or WDR82-depleted cells, indicating that PNUTS and WDR82 promote degradation of RNAPII on chromatin. Notably, reduced replication is dependent on transcription and the phospho-CTD binding protein CDC73 after depletion of PNUTS/WDR82. Altogether, our results suggest that RNAPII-CTD dephosphorylation is required for the continuous turnover of RNAPII on chromatin, thereby preventing T-R conflicts.

• Sneeggen, Marte; Pedersen, Nina Marie; Campsteijn, Coen; Haugsten, Ellen Margrethe; Stenmark, Harald & Schink, Kay Oliver (2019). WDFY2 restrains matrix metalloproteinase secretion and cell invasion by controlling VAMP3-dependent recycling. Nature Communications. 10(1), p. 1–20. doi: 10.1038/s41467-019-10794-w. Full text in Research Archive Show summary

  Cancer cells secrete matrix metalloproteinases to remodel the extracellular matrix, which enables them to overcome tissue barriers and form metastases. The membrane-bound matrix metalloproteinase MT1-MMP (MMP14) is internalized by endocytosis and recycled in endosomal compartments. It is largely unknown how endosomal sorting and recycling of MT1-MMP are controlled. Here, we show that the endosomal protein WDFY2 controls the recycling of MT1-MMP. WDFY2 localizes to endosomal tubules by binding to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns3P). We identify the v-SNARE VAMP3 as an interaction partner of WDFY2. WDFY2 knockout causes a strong redistribution of VAMP3 into small vesicles near the plasma membrane. This is accompanied by increased, VAMP3-dependent secretion of MT1-MMP, enhanced degradation of extracellular matrix, and increased cell invasion. WDFY2 is frequently lost in metastatic cancers, most predominantly in ovarian and prostate cancer. We propose that WDFY2 acts as a tumor suppressor by serving as a gatekeeper for VAMP3 recycling.

• Feng, Haiyang; Raasholm, Martina; Moosmann-Schulmeister, Alexand; Campsteijn, Coen & Thompson, Eric (2019). Switching of INCENP paralogs controls transitions in mitotic chromosomal passenger complex functions. Cell Cycle. ISSN 1538-4101. 18(17), p. 2006–2025. doi: 10.1080/15384101.2019.1634954. Full text in Research Archive Show summary

  A single inner centromere protein (INCENP) found throughout eukaryotes modulates Aurora B kinase activity and chromosomal passenger complex (CPC) localization, which is essential for timely mitotic progression. It has been proposed that INCENP might act as a rheostat to regulate Aurora B activity through mitosis, with successively higher activity threshold levels for chromosome alignment, the spindle checkpoint, anaphase spindle transfer and finally spindle elongation and cytokinesis. It remains mechanistically unclear how this would be achieved. Here, we reveal that the urochordate, Oikopleura dioica, possesses two INCENP paralogs, which display distinct localizations and subfunctionalization in order to complete M-phase. INCENPa was localized on chromosome arms and centromeres by prometaphase, and modulated Aurora B activity to mediate H3S10/S28 phosphorylation, chromosome condensation, spindle assembly and transfer of the CPC to the central spindle. Polo-like kinase (Plk1) recruitment to CDK1 phosphorylated INCENPa was crucial for INCENPa-Aurora B enrichment on centromeres. The second paralog, INCENPb was enriched on centromeres from prometaphase, and relocated to the central spindle at anaphase onset. In the absence of INCENPa, meiotic spindles failed to form, and homologous chromosomes did not segregate. INCENPb was not required for early to mid M-phase events but became essential for the activity and localization of Aurora B on the central spindle and midbody during cytokinesis in order to allow abscission to occur. Together, our results demonstrate that INCENP paralog switching on centromeres modulates Aurora B kinase localization, thus chronologically regulating CPC functions during fast embryonic divisions in the urochordate O. dioica.

• Houthaeve, Gaëlle; Xiong, Ranhua; Robijns, Joke; Luyckx, Bert; Beulque, Yasmine & Brans, Toon [Show all 12 contributors for this article] (2018). Targeted perturbation of nuclear envelope integrity with vapor nanobubble-mediated photoporation. ACS Nano. ISSN 1936-0851. 12(8), p. 7791–7802. doi: 10.1021/acsnano.8b01860. Full text in Research Archive
• Christ, Liliane Florence; Raiborg, Camilla; Wenzel, Eva; Campsteijn, Coen & Stenmark, Harald Alfred (2017). Cellular Functions and Molecular Mechanisms of the ESCRT Membrane-Scission Machinery. TIBS -Trends in Biochemical Sciences. Regular ed.. ISSN 0968-0004. 42(1), p. 42–56. doi: 10.1016/j.tibs.2016.08.016. Full text in Research Archive
• Nahse, Viola; Christ, Liliane Florence; Stenmark, Harald Alfred & Campsteijn, Coen (2017). The Abscission Checkpoint: Making It to the Final Cut. Trends in Cell Biology. ISSN 0962-8924. 27(1), p. 1–11. doi: 10.1016/j.tcb.2016.10.001. Full text in Research Archive
• Christ, Liliane Florence; Wenzel, Eva; Liestøl, Knut; Raiborg, Camilla; Campsteijn, Coen & Stenmark, Harald Alfred (2016). ALIX and ESCRT-I/II function as parallel ESCRT-III recruiters in cytokinetic abscission. Journal of Cell Biology. ISSN 0021-9525. 212(5), p. 499–513. doi: 10.1083/jcb.201507009. Full text in Research Archive
• Campsteijn, Coen; Vietri, Marina & Stenmark, Harald Alfred (2016). Novel ESCRT functions in cell biology: Spiraling out of control? Current Opinion in Cell Biology. ISSN 0955-0674. 41, p. 1–8. doi: 10.1016/j.ceb.2016.03.008. Full text in Research Archive
• Vietri, Marina; Stenmark, Harald Alfred & Campsteijn, Coen (2016). Closing a gap in the nuclear envelope. Current Opinion in Cell Biology. ISSN 0955-0674. 40, p. 90–97. doi: 10.1016/j.ceb.2016.03.001. Full text in Research Archive
• Subramaniam, Gunasekaran; Campsteijn, Coen & Thompson, Eric (2015). Co-expressed Cyclin D variants cooperate to regulate proliferation of germline nuclei in a syncytium. Cell Cycle. ISSN 1538-4101. 14(13), p. 2129–2141. doi: 10.1080/15384101.2015.1041690. Full text in Research Archive Show summary

  The role of the G1-phase Cyclin D-CDK 4/6 regulatory module in linking germline stem cell (GSC) proliferation to nutrition is evolutionarily variable. In invertebrate Drosophila and C. elegans GSC models, G1 is nearly absent and Cyclin E is expressed throughout the cell cycle, whereas vertebrate spermatogonial stem cells have a distinct G1 and Cyclin D1 plays an important role in GSC renewal. In the invertebrate, chordate, Oikopleura, where germline nuclei proliferate asynchronously in a syncytium, we show a distinct G1-phase in which 2 Cyclin D variants are co-expressed. Cyclin Dd, present in both somatic endocycling cells and the germline, localized to germline nuclei during G1 before declining at G1/S. Cyclin Db, restricted to the germline, remained cytoplasmic, co-localizing in foci with the Cyclin-dependent Kinase Inhibitor, CKIa. These foci showed a preferential spatial distribution adjacent to syncytial germline nuclei at G1/S. During nutrient-restricted growth arrest, upregulated CKIa accumulated in arrested somatic endoreduplicative nuclei but did not do so in germline nuclei. In the latter context, Cyclin Dd levels gradually decreased. In contrast, the Cyclin Dbb splice variant, lacking the Rb-interaction domain and phosphodegron, was specifically upregulated and the number of cytoplasmic foci containing this variant increased. This upregulation was dependent on stress response MAPK p38 signaling. We conclude that under favorable conditions, Cyclin Dbb-CDK6 sequesters CKIa in the cytoplasm to cooperate with Cyclin Dd-CDK6 in promoting germline nuclear proliferation. Under nutrient-restriction, this sequestration function is enhanced to permit continued, though reduced, cycling of the germline during somatic growth arrest.

• Øvrebø, Jan Inge; Campsteijn, Coen; Kourtesis, Ioannis; Hausen, Harald; Raasholm, Martina & Thompson, Eric (2015). Functional specialization of chordate cdk1 paralogs during oogenic meiosis. Cell Cycle. ISSN 1538-4101. 14(6), p. 880–893. doi: 10.1080/15384101.2015.1006000. Full text in Research Archive
• Vietri, Marina; Schink, Kay Oliver; Campsteijn, Coen; Wegner, Catherine E Sem; Schultz, Sebastian & Christ, Liliane Florence [Show all 10 contributors for this article] (2015). Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. Nature. ISSN 0028-0836. 522(7555), p. 231–235. doi: 10.1038/nature14408. Full text in Research Archive
• Danks, Gemma Barbara; Raasholm, Martina; Campsteijn, Coen; Long, Abby M.; Manak, J Robert & Lenhard, Boris [Show all 7 contributors for this article] (2015). Trans-splicing and operons in metazoans: Translational control in maternally regulated development and recovery from growth arrest. Molecular Biology and Evolution (MBE). ISSN 0737-4038. 32(3), p. 585–599. doi: 10.1093/molbev/msu336. Full text in Research Archive
• Salvi, Mauro; Raiborg, Camilla; Hanson, Phyllis I.; Campsteijn, Coen; Stenmark, Harald & Pinna, Lorenzo A. (2014). CK2 involvement in ESCRT-III complex phosphorylation. Archives of Biochemistry and Biophysics. ISSN 0003-9861. 545, p. 83–91. doi: 10.1016/j.abb.2014.01.006. Full text in Research Archive
• Subramaniam, Gunasekaran; Campsteijn, Coen & Thompson, Eric (2014). Lifespan extension in a semelparous chordate occurs via developmental growth arrest just prior to meiotic entry. PLOS ONE. 9(4:e93787). doi: 10.1371/journal.pone.0093787. Full text in Research Archive Show summary

  It is proposed that the ageing process is linked to signaling from the germline such that the rate of ageing can be adjusted to the state of the reproductive system, allowing these two processes to co-evolve. Mechanistic insight into this link has been primarily derived from iteroparous reproductive models, the nematode C. elegans, and the arthropod Drosophila. Here, we examined to what extent these mechanisms are evolutionarily conserved in a semelparous chordate, Oikopleura dioica, where we identify a developmental growth arrest (GA) in response to crowded, diet-restricted conditions, which can extend its lifespan at least three-fold. Under nutritional stress, the iteroparative models sacrifice germ cells that have entered meiosis, while maintaining a reduced pool of active germline stem cells (GSCs). In contrast, O. dioica only entered GA prior to meiotic entry. Stress conditions encountered after this point led to maturation in a normal time frame but with reduced reproductive output. During GA, TOR signaling was inhibited, whereas MAPK, ERK1/2 and p38 pathways were activated, and under such conditions, activation of these pathways was shown to be critical for survival. Direct inhibition of TOR signaling alone was sufficient to prevent meiotic entry and germline differentiation. This inhibition activated the p38 pathway, but did not activate the ERK1/2 pathway. Thus, the link between reproductive status and lifespan extension in response to nutrientlimited conditions is interpreted in a significantly different manner in these iteroparative versus semelparous models. In the latter case, meiotic entry is a definitive signal that lifespan extension can no longer occur, whereas in the former, meiotic entry is not a unique chronological event, and can be largely erased during lifespan extension in response to nutrient stress, and reactivated from a pool of maintained GSCs when conditions improve.

• Thoresen, Sigrid Bratlie; Campsteijn, Coen; Vietri, Marina; Schink, Kay Oliver; Liestøl, Knut & Andersen, Jens S. [Show all 8 contributors for this article] (2014). ANCHR mediates Aurora-B-dependent abscission checkpoint control through retention of VPS4. Nature Cell Biology. ISSN 1465-7392. 16(6), p. 547–557. doi: 10.1038/ncb2959. Full text in Research Archive
• Danks, Gemma Barbara; Campsteijn, Coen; Parida, Mruyunjaya; Butcher, Stephen; Doddapaneni, Harsha & Fu, Bolei [Show all 13 contributors for this article] (2013). OikoBase: a genomics and developmental transcriptomics resource for the urochordate Oikopleura dioica. Nucleic Acids Research (NAR). ISSN 0305-1048. 41(D1), p. D845–D853. doi: 10.1093/nar/gks1159. Full text in Research Archive Show summary

  We report the development of OikoBase (http://oikoarrays.biology.uiowa.edu/Oiko/), a tiling array-based genome browser resource for Oikopleura dioica, a metazoan belonging to the urochordates, the closest extant group to vertebrates. OikoBase facilitates retrieval and mining of a variety of useful genomics information. First, it includes a genome browser which interrogates 1260 genomic sequence scaffolds and features gene, transcript and CDS annotation tracks. Second, we annotated gene models with gene ontology (GO) terms and InterPro domains which are directly accessible in the browser with links to their entries in the GO (http://www.geneontology.org) and InterPro (http://www.ebi.ac.uk/interpro/) databases, and we provide transcript and peptide links for sequence downloads. Third, we introduce the transcriptomics of a comprehensive set of developmental stages of O. dioica at high resolution and provide download- able gene expression data for all developmental stages. Fourth, we incorporate a BLAST tool to identify homologs of genes and proteins. Finally, we include a tutorial that describes how to use OikoBase as well as a link to detailed methods, explaining the data generation and analysis pipeline. OikoBase will provide a valuable resource for research in chordate development, genome evolution and plasticity and the molecular ecology of this important marine planktonic organism.

• Yadetie, Fekadu; Butcher, Stephen; Førde, Hilde Elise Sundsøy; Campsteijn, Coen; Bouquet, Jean-Marie & Karlsen, Odd Andre [Show all 12 contributors for this article] (2012). Conservation and divergence of chemical defense system in the tunicate Oikopleura dioica revealed by genome wide response to two xenobiotics. BMC Genomics. 13. doi: 10.1186/1471-2164-13-55. Full text in Research Archive Show summary

  Background Animals have developed extensive mechanisms of response to xenobiotic chemical attacks. Although recent genome surveys have suggested a broad conservation of the chemical defensome across metazoans, global gene expression responses to xenobiotics have not been well investigated in most invertebrates. Here, we performed genome survey for key defensome genes in Oikopleura dioica genome, and explored genome-wide gene expression using high density tiling arrays with over 2 million probes, in response to two model xenobiotic chemicals - the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) the pharmaceutical compound Clofibrate (Clo). Results Oikopleura genome surveys for key genes of the chemical defensome suggested a reduced repertoire. Not more than 23 cytochrome P450 (CYP) genes could be identified, and neither CYP1 family genes nor their transcriptional activator AhR was detected. These two genes were present in deuterostome ancestors. As in vertebrates, the genotoxic compound BaP induced xenobiotic biotransformation and oxidative stress responsive genes. Notable exceptions were genes of the aryl hydrocarbon receptor (AhR) signaling pathway. Clo also affected the expression of many biotransformation genes and markedly repressed genes involved in energy metabolism and muscle contraction pathways. Conclusions Oikopleura has the smallest number of CYP genes among sequenced animal genomes and lacks the AhR signaling pathway. However it appears to have basic xenobiotic inducible biotransformation genes such as a conserved genotoxic stress response gene set. Our genome survey and expression study does not support a role of AhR signaling pathway in the chemical defense of metazoans prior to the emergence of vertebrates.

• Campsteijn, Coen; Øvrebø, Jan Inge; Karlsen, Bård Ove & Thompson, Eric (2012). Expansion of cyclin D and CDK1 paralogs in Oikopleura dioica, a chordate employing diverse cell cycle variants. Molecular Biology and Evolution (MBE). ISSN 0737-4038. 29(2), p. 487–502. doi: 10.1093/molbev/msr136. Full text in Research Archive
• Moosmann-Schulmeister, Alexand; Campsteijn, Coen; Jansen, Pascal W. T. C.; Nasrallah, Carole; Raasholm, Martina & Stunnenberg, Henk G. [Show all 7 contributors for this article] (2011). Histone variant innovation in a rapidly evolving chordate lineage. BMC Evolutionary Biology. 11. doi: 10.1186/1471-2148-11-208. Full text in Research Archive Show summary

  Background: Histone variants alter the composition of nucleosomes and play crucial roles in transcription, chromosome segregation, DNA repair, and sperm compaction. Modification of metazoan histone variant lineages occurs on a background of genome architecture that shows global similarities from sponges to vertebrates, but the urochordate, Oikopleura dioica, a member of the sister group to vertebrates, exhibits profound modification of this ancestral architecture. Results: We show that a histone complement of 47 gene loci encodes 31 histone variants, grouped in distinct sets of developmental expression profiles throughout the life cycle. A particularly diverse array of 15 male-specific histone variants was uncovered, including a testes-specific H4t, the first metazoan H4 sequence variant reported. Universal histone variants H3.3, CenH3, and H2A.Z are present but O. dioica lacks homologs of macroH2A and H2AX. The genome encodes many H2A and H2B variants and the repertoire of H2A.Z isoforms is expanded through alternative splicing, incrementally regulating the number of acetylatable lysine residues in the functionally important N-terminal “charge patch”. Mass spectrometry identified 40 acetylation, methylation and ubiquitylation posttranslational modifications (PTMs) and showed that hallmark PTMs of “active” and “repressive” chromatin were present in O. dioica. No obvious reduction in silent heterochromatic marks was observed despite high gene density in this extraordinarily compacted chordate genome. Conclusions: These results show that histone gene complements and their organization differ considerably even over modest phylogenetic distances. Substantial innovation among all core and linker histone variants has evolved in concert with adaptation of specific life history traits in this rapidly evolving chordate lineage. Keywords: histone complement, DNA repair, urochordate, posttranslational modification, endocycle, gametogenesis, testes, H2A.Z, alternative splicing

• Denoeud, France; Henriet, Simon; Mungpakdee, Sutada; Aury, Jean-Marc; Silva, Corinne Da & Brinkmann, Henner [Show all 56 contributors for this article] (2010). Plasticity of Animal Genome Architecture Unmasked by Rapid Evolution of a Pelagic Tunicate. Science. ISSN 0036-8075. 330(6009), p. 1381–1385. doi: 10.1126/science.1194167. Full text in Research Archive Show summary

  Cong, Evelyne Huynh: Oppgir Sars i kilden, men har ikke norsk fødselsnr, og kan derfor ikke kreditere UiB./tøf

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• Chand, Prem; Gomes, Tania; Song, You; Georgantzopoulou, Anastasia; Jha, Awadesh & Campsteijn, Coen [Show all 7 contributors for this article] (2025). Comprehensive Characterization of RainbowTrout Hepatic 3D Spheroids Using Microscopyand a Multimode Detection Platform. Full text in Research Archive
• Hultman, Maria Thérése; Chand, Prem; Gomes, Tania; Song, You; Georgantzopoulou, Anastasia & Campsteijn, Coen [Show all 7 contributors for this article] (2025). Comprehensive Characterization of Rainbow Trout Hepatic 3D Spheroids: Morphological and Transcriptional Insights. Full text in Research Archive
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