Cellular & Molecular Imaging

Low-grade serous carcinoma (LGSOC) of the ovary or peritoneum is a rare type of epithelial ovarian cancer with unique molecular and clinical characteristics compared to the more common High-grade serous ovarian carcinoma (HGSOC) subtype. All pivotal clinical trials guiding management of epithelial ovarian carcinoma are over representative of HGSOC, thus findings cannot be unconditionally extrapolated to rarer chemo-resistant subtypes such as LGSOC. No standard-of-care treatments are established for recurrent LGSOC hence we conducted the largest quantitative high-throughput drug screening effort (n=3436 compounds) across a panel of 12 patient-derived LGSOC cell lines and one normal ovary cell line to identify unexplored therapeutic avenues. Using a combination of high-throughput robotics, high-content imaging and novel data analysis pipelines our data set identified 67 high and 24 moderate confidence hits which induced cancer cell specific cytotoxicity at the lowest compound dose assessed (0.1µM). We also revealed a series of novel drug classes (mTOR/PI3K/AKT, EGFR and MDM2-p53) in which LGSOC cell lines were highly susceptible to.

This is a benchmark dataset used to develop and test a new metric for quantitatively describing vacuome organization in developing root tissues. Reference: Kočová H, Caldarescu GA, Bezvoda R, Cvrčková F: The Tonoplast Topology Index - a new metric for describing vacuole organization. Manuscript in preparation/to be submitted to biorXiv.

Tara Expeditions are global scientific voyages that probe morphological and molecular diversity, evolution and ecology of marine plankton to explore how they are impacted by changes in the Earth's climate. The first expeditions collected samples of marine plankton containing viruses, bacteria, archaea, protists and planktonic metazoans living in the photic layer of the world's oceans. These expeditions, the first taking place between 2009 and 2013, include Tara Oceans: a global view, and Tara Oceans Polar Circle, both of which followed the same sampling protocol. This dataset includes 1074 pictures of 284 planktonic taxa (mainly microalgae and other Ciliate and Radiolarian protists) collected from the vicinity of the Marquesas Islands in the Southern Pacific Ocean during the Tara Oceans expedition. Multiple samples particularly of the size fractions 5-20 and 20 180 um from four sites and two depths were processed with different methods and studied in detail using scanning electron microscopy.

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Chronic Pseudomonas aeruginosa lung infection is a major cause of morbidity and mortality in people with lung disease. Once established, infection is rarely eradicated and often persists despite prolonged antimicrobial therapy, but the mechanisms that support persistence in the human lung remain poorly understood. To define how P. aeruginosa occupies and adapts to diseased lung tissue, we applied host–pathogen spatial transcriptomics to explanted and resected lungs from people with Cystic Fibrosis (CF) and chronic obstructive pulmonary disease (COPD), mapping bacterial niches and transcriptional states in situ.

This dataset comprises transmission electron microscopy (TEM) images of kidney (glomeruli and podocytes) from mice with podocyte-specific knockout of IRE1α (IRE1α flox/flox; Cre) and control mice, with or without adriamycin (doxorubicin)-induced nephrosis. Images are organised into per-kidney subfolders labelled by mouse number, genotype (KO or control) and treatment (adriamycin/doxorubicin or untreated); magnification is referenced in each file name. See associated publications for details.

Reprocessed images from LINCS image dataset and Human Protein Atlas for training deep learning models.

Background Microsporidia sp. MB, a microsporidian symbiont found naturally in Anopheles mosquitoes, has potential as a novel malaria control tool since it can inhibit Plasmodium development and transmission. The most feasible MB-based Plasmodium control strategy would involve dissemination through live mosquito releases, or release of spores infective to mosquito larvae. To implement either strategy, establishment of stable mosquito colonies carrying MB at a high frequency is likely to be essential. The progeny of field caught An. gambiae s.l from Burkina Faso were isolated for individual egg laying and tested for MB. The progeny of the MB positive females were pooled and this process was repeated for multiple generations. The relative density of MB in different life stages and tissues of the An. coluzzii host was examined using a novel duplex qPCR assay. We also examined the impact of MB on fecundity through individualization for egg laying and counting of eggs. Finally, we examined laid eggs for presence of MB spores. Results Three An. coluzzii colonies and one An. gambiae s.l hybrid colony were established with high prevalence and density of MB and were maintained for more than two years with minimal intervention. MB prevalence and density was highest in eggs and adult females and lowest in L4 larvae; in adults density was highest in the gonads. Additionally, MB density increased in ovary samples following blood feeding which was likely due to the activation of sporogony. The production of spores is the reason why MB-carrying females lay more white non-hatching eggs and show a small reduction in fecundity. Conclusions Establishment of several stable MB carrying An. gambiae s.l colonies and understanding the impact of spores on fecundity are significant steps forward in developing MB as a malaria control tool.

Accurate transition into mitosis driven by cyclin B1-CDK1 activity is essential to avoid chromosome segregation errors and preserve genome integrity. How this activity is spatially controlled to trigger mitotic onset remains unclear. Here, we show that chromosome condensation triggers an increase in nuclear envelope (NE) tension. This increased tension is required for translocation of cyclin B1 into the nucleus and dynein loading on nuclear pore complexes (NPCs), ensuring timely mitotic entry. Micromanipulation experiments further indicate this tension-dependent mechanism requires SUN proteins on the NE. Disruption of chromosome condensation leads to an accumulation of the G2 checkpoint kinase Wee1 and inhibition of CDK1 activity, which result in a temporary delay in mitotic entry. This delay can be overridden by increasing tension on the NE, which accelerates the nuclear translocation of cyclin B1 and dynein loading. We propose that mitotic onset is controlled by a chromosome-dependent NE tension mechanism that enables robust spatiotemporal coupling between chromosome condensation and the structural changes required for an efficient mitosis.

Fetal hematopoiesis takes place in the liver before colonizing the bone marrow where it will persist for life. This colonization is thought to be mediated by specification of a microenvironment that selectively recruits hematopoietic cells to the nascent bone marrow. The identity and mechanisms regulating the specification of this “colonization niche” are unclear. Here we identify a VCAM1+ sinusoidal colonization niche in the diaphysis that regulates neutrophil and hematopoietic stem cell colonization of the bone marrow. Using confocal microscopymicroscopy, we found that colonizing hematopoietic stem and progenitor cells (HSPC) and myeloid cells selectively localize to a subset of VCAM1+ sinusoids in the center of the diaphysis. Vcam1 deletion in endothelial cells impaired hematopoietic colonization while depletion of yolk-sac-derived osteoclasts abrogateddisrupted VCAM1+ expression, resulting in impaired and neutrophil and HSPC colonization ofto the bone marrow. Unexpectedly, depletion of yolk-sac-derived myeloid cells also increased fetal liver hematopoietic stem cell numbers, function and erythropoiesis in an osteoclast-independent mannerof osteoclast activity. Thus, the yolk sac produces two different types of myeloid cells in different organs that have oppositedistinct roles in regulating fetal hematopoiesis: while yolk-sac derived myeloid cells in the bone marrow promote hematopoietic colonization by specifying a VCAM1+ colonization niche, a different subset of yolk-sac-derived myeloid cells inhibitsregulates HSC in the fetal liverfetal liver hematopoiesis.