Bone vasculature provides protection and signals necessary to control stem cell quiescence and renewal (1). Specifically, type H capillaries, which highly express Endomucin, constitute the endothelial niche supporting a microenvironment of osteoprogenitors and long term hematopoietic stem cells (2 - 4). The age dependent decline in type H endothelial cells was shown to be associated with bone dysregulation

Mammalian haploid somatic cells are unstable and prone to diploidize, but the cause of haploid instability remains largely unknown. Previously, we found that mammalian haploid somatic cells suffer chronic centrosome loss stemming from the uncoupling of DNA replication and centrosome duplication cycles. However, the lack of methodology to restore the coupling between DNA replication and centrosome duplication

Contact inhibition of locomotion (CIL), in which cells repolarize and move away from contact, is now established as a fundamental driving force in development, repair, and disease biology. Much of what we know of CIL stems from studies on 2D substrates that fail to provide an essential biophysical cue - the curvature of extracellular matrix fibers. We discover rules controlling outcomes of cell-cell

Two main systems regulate the plasmalemma tension and provide a close connection of the protoplast with the cell wall in fungi: turgor pressure and actin cytoskeleton. These systems work together with the plasmalemma focal adhesion to the cell wall and their contribution to fungal cell organization has been partially studied, but remains controversial in model filamentous ascomycetes and oomycetes

AMP-activated protein kinase (AMPK) is a multifunctional kinase that regulates microtubule (MT) dynamic instability through CLIP-170 phosphorylation; however, its physiological relevance in vivo remains to be elucidated. In this study, we identified an active form of AMPK localized at the intercalated discs in the heart, a specific cell-cell junction present between cardiomyocytes. A contractile inhibitor

Cytokinesis in land plants involves the formation of a cell plate that develops into the new cell wall. Callose is a β-1,3 glucan that transiently accumulates at later stages of cell plate development and is thought to stabilize the delicate membrane network of the cell plate as it expands. Cytokinetic callose deposition is currently considered specific to multicellular plant species as it has not

The Drosophila IAP protein, DIAP2, is a key mediator of NF-kappaB signalling and innate immune responses in the fly. DIAP2 is required for both local immune activation, taking place in the epithelial cells of the gut and trachea, and for mounting systemic immune responses in the cells of the fat body. We found that transgenic expression of DIAP2 leads to a spontaneous induction of NF-kappaB target

Dendritic actin networks develop from a first actin filament through branching by the Arp2/3 complex. At the surface of endosomes, the WASH complex activates the Arp2/3 complex and interacts with the Capping Protein for unclear reasons. Here we show that that the WASH complex interacts with Dynactin and uncaps it through its FAM21 subunit. In vitro, the uncapped Arp1/11 minifilament elongates an actin

Domain of Unknown Function (DUF) genes are broadly conserved in metazoa but have an unknown biological function. Previously, we established transcriptional profiles of the germline and stem cells of the flatworm Macrostomum lignano (Grudniewska et al., 2016). Here, we used this information to probe the function of DUF genes in M. lignano. Recently, Kang et al. (2016) found that DUF2366 is a mitochondrial

Coronavirus disease 2019 (COVID19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originating in Wuhan China in 2019. The disease is notably severe in elderly and those with underlying chronic conditions. A molecular mechanism that explains why the elderly are vulnerable and why children are resistant is largely unknown. Understanding these differences

Commercial live cell imaging systems represent a large financial burden to research groups, while current open source incubator microscopy systems lack adaptability and are sometimes inadequate for complex imaging experimentation. We present here a low-cost microscope designed for inclusion within a conventional tissue culture incubator. The build is constructed using an entry level 3D printer as the

Iron chelating agents derived from bacterial siderophores were originally used for iron overload syndromes but have recently been investigated for cancer therapy. While systemic administration of iron chelating agents induces undesirable side effects, bacteria as a source of siderophores could potentially act as local chelator that is tumor-targeted and amplifies its impact through preferential accumulation

During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function in that impacts mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs), but the relationship between MuSCs and neural control has not been established. Herein, using a combination of single-cell transcriptomic

Cell migration is essential to most living organisms. Single cell migration involves two distinct mechanisms, either a focal adhesion- and traction-dependent mesenchymal motility or an adhesion-independent but contractility-driven propulsive amoeboid locomotion. Cohesive migration of a group of cells, also called collective cell migration, has been only described as an adhesion- and traction-dependent

Intrahepatic bile ducts are lined by biliary epithelial cells (BECs). However, defining the genetic heterogeneity of BECs remains challenging, and tools for identifying BEC subpopulations are limited. Here, we characterize Sox9EGFP transgene expression in the liver and demonstrate that GFP expression levels are associated with distinct cell types. BECs express low or high levels of GFP, while periportal

We present a software-assisted workflow for the alignment and matching of filamentous structures across a 3D stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After an initial alignment, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. Supported by a visual quality assessment

PA28γ, a nuclear activator of the 20S proteasome, is involved in the degradation of several proteins regulating cell proliferation, but its precise cellular functions remain unclear. Here, we show that PA28γ is crucial for chromatin compaction. In human cells, we find that a small fraction of PA28γ co-localizes with HP1β, and PA28γ is present at HP1β-containing repetitive-DNA regions. PA28γ-depletion

A cytoskeletal protein keratin 19 (K19) is highly expressed in breast cancer but its effects on breast cancer cell mechanics are unclear. Using KRT19 knockout (KO) cells and cells where K19 expression was rescued, we found that K19 is required to maintain rounded epithelial-like shape and tight cell-cell adhesion of MCF7 cells. A loss of K19 resulted in a lower level of plakoglobin and internalization

Modulation of the host cell is integral to the survival and replication of microbial pathogens. Several intracellular bacterial pathogens deliver a cohort of bacterial proteins, termed effector proteins into the host cell during infection by sophisticated protein translocation systems which manipulate cellular processes and functions. Despite the importance of these proteins during infection the functional

Clinical progression of tauopathies is reflected by the transcellular propagation of pathogenic Tau seeds with the possible involvement of extracellular vesicles as transport vectors. However, the mechanism regulating extracellular vesicle cargo delivery to recipient cells is poorly understood. We established a cell model for investigating extracellular vesicle-delivery of membranes and proteins. In

Introduction: Glutathione deficiency and chronic bacterial inflammation exacerbates the oxidative stress damage to airways in cystic fibrosis. Improvements to current antioxidant therapeutic strategies are needed. Dietary supplement, γ-glutamylcysteine (GGC), the immediate precursor to glutathione, rapidly boosts cellular glutathione levels following a single dose in healthy individuals. Efficacy of

Between 6-20% of the cellular proteome is under circadian control to tune cell function with cycles of environmental change. For cell viability, and to maintain volume within narrow limits, the osmotic pressure exerted by changes in the soluble proteome must be compensated. The mechanisms and consequences underlying compensation are not known. Here, we show in cultured mammalian cells and in vivo that

WNT/CTNNB1 signaling regulates tissue development and homeostasis in all multicellular animals. Multiple aspects of the underlying molecular mechanism remain poorly understood and critical information on endogenous WNT/CTNNB1 signaling dynamics is missing. Here we combine CRISPR/Cas9-mediated genome editing and quantitative live-cell microscopy to measure diffusion characteristics of fluorescently

Rapid cryo-preservation of biological specimens is the gold standard for visualising cellular structures in their true structural context. However, current commercial cryo-fluorescence microscopes are limited to low resolutions. To fill this gap, we have developed cryoSIM, a microscope for 3D super-resolution fluorescence cryo-imaging for correlation with cryo electron microscopy or cryo soft X-ray

Extracellular vesicles (EVs) are emerging as a universal means of cell to cell communication and hold great potential in diagnostics and regenerative therapies. An urgent need in the field is a fundamental understanding of physiological mechanisms driving EV generation and function. Ciliary EVs act as signaling devices in Chlamydomonas and C. elegans. Mammalian cilia shed EVs to eliminate unwanted

Activin A functions in BMP signaling in two ways: it either engages ACVR1B to activate Smad2/3 signaling or binds ACVR1 to form a non-signaling complex (NSC). Although the former property has been studied extensively, the roles of the NSC remain unexplored. The genetic disorder fibrodysplasia ossificans progressiva (FOP) provides a unique window into ACVR1/Activin A signaling because in that disease

Senile plaque is one of the most prominent pathological hallmarks of Alzheimer's disease (AD). However, the mechanism governing the generation of senile plaques remains a mystery. Many researchers believed that senile plaques are derived from neuronal cells, however, there is also strong evidence showing that senile plaques are linked with cerebral microhemorrhage. We analyzed the major neural markers

Histone lysine crotonylation (Kcr), an evolutionarily conserved and widely expressed non-acetyl short-chain lysine acylation, plays important roles in transcriptional regulation and disease development. However, its genome-wide distribution, correlation with gene expression, and dynamic changes during developmental processes are largely unknown. In this study, we find that histone Kcr is mainly distributed

The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly translated to clinical care. Unfortunately, traditional drug discovery methods have a >90% failure rate and can take 10-15 years from target identification to clinical use. In contrast, drug repurposing can significantly accelerate

Autophagy is controlled in part by the repression and activation of Autophagy-related (ATG) gene transcription. Here, we demonstrate that the conserved Cdk8 Kinase Module (CKM) of the mediator complex represses transcription of several ATG genes. To relieve this repression following nitrogen starvation, Med13 is rapidly degraded via a novel selective autophagy mechanism. This pathway requires the core

Live cell imaging using DNA-binding fluorescent probes is an essential molecular tool in various biological and biomedical fields. The major challenges in currently used DNA probes are to avoid UV light photo-excitation with high DNA selectivity and cell-permeability and are the availability of the cutting-edge imaging techniques such as a super-resolution microscopy. Herein we report new orange to

Reverse transcription quantitative PCR (RT-qPCR) is used to quantify gene expression and require standardization with reference genes. We sought to identify the reference genes best suited for experiments that induce osteogenic differentiation from human induced pluripotent stem (iPS) cells. They were cultured in an undifferentiated maintenance medium and after confluence, further cultured in an osteogenic

Porosomes are cup-shaped lipoprotein structures at the cell plasma membrane involved in fractional release of intra-vesicular contents during secretion. At the base of the porosome facing the cell cytoplasm, secretory vesicles dock, fuse and swell, to release intra-vesicular content during secretion. Earlier studies demonstrate the cystic fibrosis trans-membrane conductance regulator (CFTR) associated

The membrane transport apparatus comprises a series of separate membrane bound compartments, or transport stations, that are responsible for the synthesis, processing, transport, sorting and delivery to their final cellular destinations of most transmembrane and soluble lumenal proteins. Over the last decades the membrane transport system has been shown to be extensively regulated both by environmental

We present a quantitative co-analysis of RNA abundance and sarcomere organization in single cells and an integrated framework to predict subcellular organization states from gene expression. We used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes expressing mEGFP-tagged alpha-actinin-2 to develop quantitative image analysis tools for systematic and automated classification of subcellular

About half the world's population is at risk of malaria, with Plasmodium falciparum malaria being responsible for the most malaria related deaths globally. Antimalarial drugs such as chloroquine and artemisinin are directed towards the proliferating intra-erythrocytic stages of the parasite, which is responsible for all the clinical symptoms of the disease. These antimalarial drugs have been reported

Glycolysis is a fundamental metabolic pathway for glucose catabolism across biology, and glycolytic enzymes are amongst the most abundant proteins in cells. Their expression at such levels provides a particular challenge. Here we demonstrate that the glycolytic mRNAs are localized to granules in yeast and human cells. Detailed live cell and smFISH studies in yeast show that the mRNAs are actively translated

The flagellum of Trypanosoma brucei is a 20 micron-long organelle responsible for locomotion and cell morphogenesis. The flagellum attachment zone (FAZ) is a multi-protein complex whose function is to attach the flagellum to the cell body but also to guide cytokinesis. Cryo-transmission electron microscopy is a tool of choice to access the structure of the FAZ in a close-to-native state. However, because

The phosphatidylinositol (PI) cycle is central to eukaryotic cell signaling. Its complexity, due to the number of reactions and lipid and inositol phosphate intermediates involved makes it difficult to analyze experimentally. Computational modelling approaches are seen as a way forward to elucidate complex biological regulatory mechanisms when this cannot be achieved solely through experimental approaches

Adaptation to nutrient scarcity involves an orchestrated response of metabolic and signaling pathways to maintain homeostasis. We provide evidence that lysosomal export of cystine coordinates remobilization of internal nutrient stores with reactivation of the growth regulator TORC1 signaling upon fasting in the Drosophila fat body. Mechanistically, cystine is reduced to cysteine and metabolized to

The authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

MicroRNAs, the tiny regulators of gene expression, can be transferred between neighbouring cells via Extracellular Vesicles (EV) to control the expression of genes in both donor and recipient cells. How the Extracellular Vesicles-derived miRNAs are getting internalized and become functional in target cells is an unresolved question. We found that EV-associated miRNAs are primarily single stranded and

Coronavirus disease 2019 (COVID-19) is a disease that causes fatal disorders including severe pneumonia. To develop a therapeutic drug for COVID-19, a model that can reproduce the viral life cycle and evaluate the drug efficacy of anti-viral drugs is essential. In this study, we established a method to generate human bronchial organoids (hBO) from commercially available cryopreserved human bronchial

The mammalian cell surface is decorated with a plethora of integral membrane proteins including those required for the transport of micronutrients, such as copper, which are essential to cellular health. The concentration of micronutrients within the cell is tightly regulated to avoid their adverse deficiency and toxicity effects. The sorting and recycling of nutrients transporters within the endo-lysosomal

The trans-activation response DNA-binding protein TDP-43 regulates RNA processing and forms neuropathological aggregates in patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Investigating TDP-43 post-translational modifications, we discovered that K84 acetylation reduced nuclear import whereas K136 acetylation impaired RNA binding and splicing capabilities of TDP-43

Dopamine (DA) and norepinephrine (NE) are pivotal neuromodulators that regulate a broad range of brain functions, often in concert. Despite their physiological importance, untangling the relationship between DA and NE in finely controlling output functions is currently challenging, primarily due to a lack of techniques to visualize spatiotemporal dynamics with sufficiently high selectivity. Although

Photoperiod is an important factor of mammalian seasonal rhythm. We studied the morphological differences in HG which is a vital photosensitive organ of male striped dwarf hamsters (Cricetulus barabensis), under different photoperiods (short photoperiod, SP; moderate photoperiod, MP; long photoperiod, LP), and further investigated the molecular mechanisms related to these morphological differences

Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargoes to the membrane bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we discover a selective autophagy pathway for protein condensates formed by endocytic proteins. In this pathway, the endocytic yeast protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and

The function of the FAM83F protein, like the functions of many members of the FAM83 family, is poorly understood. Here we show that injection of Fam83f mRNA into Xenopus embryos causes axis duplication, a phenotype indicative of enhanced Wnt signalling. Consistent with this, overexpression of FAM83F activates Wnt signalling, whilst ablation of FAM83F from human colorectal cancer (CRC) cells attenuates

Knockout of the golgin giantin leads to skeletal and craniofacial defects driven by poorly studied changes in glycosylation and extracellular matrix deposition. Here, we sought to determine how giantin impacts the production of healthy bone tissue by focussing on the main protein component of the osteoid, type I collagen. Giantin mutant zebrafish accumulate multiple spontaneous fractures in their caudal

The nucleolus is essential for ribosome biogenesis and is involved in many other cellular functions. We performed a systematic spatiotemporal dissection of the human nucleolar proteome using confocal microscopy. In total, 1,318 nucleolar proteins were identified; 287 were localized to fibrillar components, and 157 were enriched along the nucleoplasmic border, indicating a potential fourth nucleolar

Two species of parasitic fungi from the phylum Chytridiomycota (chytrids) are annihilating global amphibian populations. These chytrid species-Batrachochytrium dendrobatidis and B. salamandrivorans-have high rates of mortality and transmission. Upon establishing infection in amphibians, chytrids rapidly multiply within the skin and disrupt their hosts' vital homeostasis mechanisms. Current disease

A holistic understanding of tissue and organ structures and their functions requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) makes possible the detection of up to 40 antigens and specific nucleic acids simultaneously using metal-tagged antibodies or nucleic acid probes, respectively, but has so far been restricted to two-dimensional

Throughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a population of skeletal muscle-dedicated stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, the function of MuSCs is tightly coordinated by the cellular and acellular components of their microenvironment, or the niche. While the processes that control the coupling of neurotransmission

Goblet cell metaplasia and mucus hyper-production are key features of chronic muco-obstructive lung diseases such as asthma, chronic bronchitis, and cystic fibrosis. Various mechanisms lead to goblet cell metaplasia in the airways; the driving mechanism for goblet cell metaplasia in a specific patient may be unknown. We recently found that heat shock protein 90 (HSP90) is important for both IL-13-

The pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) involves activation of the DNA damage response (DDR). However, biologic mechanisms that regulate the DDR and contribute to COPD progression are poorly understood. Because microRNAs are important regulators of the DDR, we hypothesized that microRNA expression changes cause pathologic DDR activation in COPD. Therefore, we evaluated microRNA

Successful cell division requires dramatic reorganization of the cell cortex in coordination with actomyosin cytoskeleton organization, membrane trafficking and cell adhesion. Although the contractile actomyosin ring is considered as hallmark of cytokinesis, in some cell types cell adhesion systems have been shown to drive cytokinesis independently from actomyosin function. We previously reported that

We selectively inactivated the Taf4 subunit of general transcription factor TFIID in adult murine pancreatic beta cells (BCs). Taf4 inactivation rapidly diminishes expression of critical genes involved in BC function leading to increased glycaemia, lowered blood insulin levels, defective glucose-stimulated insulin secretion and in the longer term reduced BC mass through apoptosis of a subpopulation

Heterologously-expressed bacterial nitroreductase (NTR) enzymes sensitize eukaryotic cells to prodrugs such as metronidazole (MTZ), enabling selective cell ablation paradigms that have expanded studies of cell function and regeneration in vertebrate systems. However, first-generation NTRs require confoundingly toxic prodrug treatments (e.g. 10 mM MTZ) and some cell types have proven resistant. We used

During muscle regeneration, extracellular signal-regulated kinase (ERK) promotes both proliferation and migration. However, the relationship between proliferation and migration is poorly understood in this context. To elucidate this complex relationship on a physiological level, we established an intravital imaging system for measuring ERK activity, migration speed, and cell-cycle phases in mouse muscle