Cell and Tissue Research最新文献

Liquid-liquid phase separation (LLPS) is an emerging research field in cellular biology. LLPS-driven biomolecular condensates act as reaction chambers and regulatory hubs for critical processes, including chromatin architecture, gene expression, and metabolism. The dysregulation of these processes frequently impedes the proper execution of physiological functions. Current research indicates that abnormal phase separation plays a significant role in the pathogenesis of diseases and aging. This review briefly overviews the fundamental concepts and research methods related to phase separation. We also summarize studies concerning its physiological functions, particularly emphasizing its role in hematopoiesis. We further discuss how abnormal phase separation can lead to hematological disorders, specifically summarizing its involvement in the pathogenesis of leukemia. Despite recent advancements, elucidating LLPS mechanisms in hematopoiesis remains challenging due to the intricate interplay between biomolecular condensates and cellular function. Future research efforts aiming to reveal the role of LLPS in hematological diseases hold promise for novel therapeutic interventions and a deeper understanding of hematopoietic processes.

Our current understanding of brain organization in malacostracan crustaceans is strongly biased towards representatives of the Decapoda ("ten legged" crustaceans) such as crayfish, crabs, clawed lobsters and spiny lobsters. However, to understand aspects of brain evolution in crustaceans, a broader taxonomic sampling is essential. The peracarid crustaceans are a species-rich group that embraces representatives of, e.g. the Isopoda, Amphipoda and Mysida ("opossum shrimps"), taxa whose neuroanatomy has not been carefully examined. The current study sets out to analyze brain morphology of the mysid Neomysis integer (Leach, 1814; Peracarida, Mysida) using immunohistochemistry against the presynaptic protein synapsin and the neuropeptides RFamide, SIFamide and allatostatin combined with three-dimensional reconstruction of elements of the central olfactory pathway. Furthermore, we studied the inventory of sensilla on the first pair of antennae using cuticular autofluorescence. Anterograde filling with neuronal tracers allowed visualisation the central projections of the sensilla on the first pair of antennae. This species is known to display a sexual dimorphism in both the peripheral and central olfactory pathway. We focussed our analysis on this aspect because in contrast to Hexapoda, reports on a sexual dimorphism of the olfactory system are extremely rare in malacostracan crustaceans. We provide a detailed description of the sensilla associated with a male-specific structure on the pair of first antenna the "lobus masculinus". Furthermore, we analyzed the projection patterns of theses sensilla into the "male-specific neuropil" in the deutocerebrum and critically discuss our results in comparison to examples of sexual dimorphism in the chemosensory pathways in other malacostracan crustaceans and hexapods.

Mesenchymal stromal cells (MSC) are multipotent cells that can modulate immune cells, affecting macrophages, monocytes, and lymphocytes. Neutrophils are circulating leucocytes responsible for the first line of defense and can assume different phenotypes depending on their environment: N0, the naïve form, N1 (inflammatory), N2 (anti-inflammatory). This study explores the potentially protective roles of chorionic membrane MSCs and their products-conditioned medium and pre-conditioned cMSC-derived membrane microparticles (MP-cMSC)-on neutrophils. Conditioned medium treatment reduced the rate of apoptosis and enhanced the immunosuppressive potential consistent with an anti-inflammatory profile. MP-cMSC are a noteworthy cell-free therapy, consisting of artificially generated circular lipid bilayer structures with no cargo and approximately 200 nm in size. When added to neutrophil culture, MPs increased neutral red uptake, suggesting an enhanced phagocytic activity. In the MSC co-culture group, a reduced rate of apoptosis, increased neutral red uptake, and elevated programed death-ligand 1 (PD-L1) expression were observed. These findings suggest that the distinct effects elicited by conditioned media, microparticles, and co-culture are likely influenced by the specific nature of the interactions involved-whether purely paracrine, mediated through direct cell-to-cell contact, or a combination of both.

Septoclasts (SCs), which express both fatty acid-binding protein 5 and platelet-derived growth factor beta, are mononuclear cartilage-resorbing cells predominantly located at the chondro-osseous junction of the growth plate (GP). These cells originate from pericytes (PCs). Cathepsin B (CTSB) and matrix metalloproteinase-13 (MMP13), expressed in SCs, participate in the degradation of collagen and other cartilage matrices. This study aimed to investigate the involvement of the ETS proto-oncogene 1 (ETS1) in the transcription of Ctsb and Mmp13 during the differentiation of SCs from PCs. ETS1 was localized in SCs and a small number of PCs during development and postnatal stages. Upregulation of Ets1, Mmp13, Ctsb, and the Ets1-related genes, specificity protein 1 (Sp-1), jun proto-oncogene (c-Jun), and cAMP response element-binding protein-binding protein (Crebbp) in SCs compared with those in PCs was shown by RNA-seq analysis of samples isolated from the tibiae of 3-week-old postnatal mice. The Ets1-related proteins were localized ubiquitously in SCs and PCs in the GP. In primary SC cultures, the expression levels of Ctsb and Mmp13 were significantly reduced following treatment with Ets1 siRNA. Thus, our results revealed that ETS1 promoted the expression of Ctsb and Mmp13 in SCs during the differentiation of SCs from PCs.

Pulmonary surfactant is essential for lung function and consists mainly of lipids, almost half of which in adult mammals originate from de novo synthesis in alveolar epithelial type-2 (AE2) cells. Obesogenic nutrition and hypoxia coexist in obese patients with chronic lung diseases. This study tested the hypothesis that diet-induced obesity and chronic hypoxia alter lipid metabolism and thereby deteriorate surfactant homeostasis. Male C57BL/6N mice were fed control diet (4% fat, 6% sucrose; CD), high-sucrose diet (4% fat, 46% sucrose; HSD) or high-fat diet (35% fat, 7% sucrose; HFD). After 27 weeks, half of each diet group was exposed to hypoxia (13% O₂, Hyp) for 3 weeks. After 30 weeks, lung mechanics were assessed, and the blood, livers, and lungs were analyzed. In CD-fed mice, hypoxia induced lung mechanical changes indicative of reduced elastic recoil properties, as well as smaller lamellar bodies (LBs) and higher composite body volumes, suggesting an increased surfactant precursor formation. HSD and HFD induced lipid accumulation in liver and AE2 cells. In HSD-Hyp and HFD-Hyp, LB volumes per alveolar surface area were elevated, indicating compensatory increases in intracellular surfactant pools which were absent in CD-Hyp. Additionally, hypoxia-related lung mechanics alterations were less pronounced in HSD-Hyp and HFD-Hyp. Lung proteome analysis revealed that only a few lipid metabolism-associated proteins were similarly regulated within diet groups under hypoxia, with the most prominent changes in sucrose-fed hypoxic animals. Thus, individual diet-related metabolic states specifically affect the adaptation of the pulmonary lipid metabolism and intracellular surfactant assembly to chronic hypoxia.

Olfaction plays a crucial role in distinguishing odors, enabling organisms to seek benefits and evade hazards. Olfactory receptors (ORs), characterized by highly variable binding pockets, facilitate the detection of diverse odorants from both external and internal environments. Nasal ORs, expressed in olfactory sensory neurons (OSNs), are critical for olfactory cognition and associated neuronal plasticity. In contrast, extra-nasal ORs, expressed in extra-olfactory tissues, detect specific chemicals and modulate cellular processes such as proliferation, migration, inflammation, and apoptosis. Aberrant OR expression or dysfunction has been implicated in numerous human diseases, including anosmia, dementia, dermatopathies, obesity, infertility, cancers, respiratory disorders, atherosclerosis and viral infections. Olfactory training, such as aromatherapy, demonstrates significant therapeutic potential for anosmia, dementia and psychological distress. Natural or synthetic odorants have been applied for promoting hair regeneration and cutaneous wound healing. Conversely, overexpression of specific ORs in cancer cells may drive tumor progression. Additionally, ORs may mediate virus-host interactions during infection, owing to their structural variability. Collectively, OR-targeted agonists and antagonists (odorants) represent promising candidates for treating OR-associated pathologies.

Infertility and subfertility are significant reproductive challenges in cattle, often linked to genetic factors. Among these genetic factors, the bovine Y-linked gene family, PRAMEY, has emerged as a candidate due to its involvement in germ cell formation, fertilization, and embryonic development. This study investigates PRAMEY's role in sperm-egg binding, acrosome integrity, and epigenetic modifications during fertilization and early embryogenesis. Using IVF with bovine spermatozoa treated with either PRAMEY antibody (ab) or rabbit IgG control, we assessed sperm-egg binding and acrosome integrity at 2, 4, and 6 h post-fertilization (hpf). PRAMEY ab treatment doubled sperm binding per oocyte across all time points, with a significant increase at 6 hpf (P ≤ 0.05), although no differences in acrosome integrity were observed (P > 0.05). To explore PRAMEY's role in epigenetic regulation, we analyzed DNA (5-methylcytosine (5-mC)) and histone (H3K9me3 and H3K27me3) methylation in zygotes and embryos using immunofluorescent staining techniques. Zygotes derived from PRAMEY ab-treated spermatozoa showed significantly reduced DNA methylation in paternal pronuclei at 10 hpf and maternal pronuclei at 25 hpf (P ≤ 0.01). Histone methylation analysis revealed no significant differences in H3K9me3 methylation between groups, but H3K27me3 methylation was significantly lower in embryos produced using PRAMEY ab-treated spermatozoa at the 8-cell and morula stages (P ≤ 0.05). In summary, PRAMEY inhibition enhances sperm-egg binding and influences DNA and histone methylation dynamics in bovine embryos, underscoring its potential role in fertilization and early embryonic epigenetic regulation.

The Na,K-ATPase is a vital transmembrane enzyme, which is important for maintaining cell membrane potentials and the general functionality of animal cells. The enzyme's minimal functional unit consists of one α and one β-subunit, whereas the number of existing paralogs varies in different insect species. The functional roles of different β-subunits, which can account for their diversity within a single species, are so far only partially explained. The emphasis of this study was to specifically elucidate the involvement in septate junctions of the four β-subunits of the new model system Oncopeltus fasciatus. Septate junctions function as a paracellular barrier controlling the flow of solutes across epithelia. So far, studies in Drosophila revealed that nervana2, the β2 homolog of Drosophila, is involved in septate junction formation. In O. fasciatus, we demonstrate that most of the Na,K-ATPase subunits colocalize with septate junction proteins. This agrees with our previous findings implying a role of β2 in the control of tracheal tube size in O. fasciatus, which according to the findings in Drosophila appears to be dependent on a stable formation of septate junctions. Finally, our data suggest a connection between the septate junction protein coracle and the enigmatic, N-terminally strongly truncated βx, which has no obvious homologs in other insects. Our study proposes that the four β-subunits form functional units with septate junction proteins, either allowing tissue-adjusted formation of cell-cell contacts or other yet unknown functions.

While the prolonged consumption of sucrose-containing beverages is known to impact many organs, their specific effects on the small intestine remain elusive. This study aimed to evaluate how regular intake of sucrose, in amounts typically consumed, affects goblet cells, which play a critical role in regulating the mucosal barrier and innate immune defenses in the small intestine. Ten-week-old male ddY mice, a model of diet-induced obesity, were given a regular diet with either plain water or 7% sucrose water. Caloric intake was monitored weekly through food and drink measurements. After 8 weeks, glucose and insulin responses were evaluated following an oral gavage of glucose or sucrose. At 14 weeks, plasma, whole small intestine, and liver samples were collected. Despite achieving an isocaloric state, mice drinking sucrose water showed approximately a 1.5-fold increase in body weight and impaired glucose tolerance. In the small intestine, genes involved in sucrose digestion and absorption (Sis, Sglt1, Glut2, and Glut5) were upregulated, while genes essential for maintaining the intestinal barrier and function (Epcam, Fabp2, Cldn1, Ocln, and Tjp1) were downregulated. Serum levels and mRNA expression of the inflammatory cytokine, interleukin-18 were elevated. Genes responsible for goblet cell differentiation and function (Hes1, Gfi1, Spdef, and Klf4) were downregulated, leading to an increase in immature goblet cells and a decrease in mucin-producing markers (Muc2, Muc4, and Muc13) in the jejunum. The findings underscore that besides obesity, long-term intake of sucrose-containing drinks provokes localized inflammation and disrupts small intestinal barrier function by impairing goblet cell differentiation and activity.

During type 1 diabetes (T1D), oxidative stress in beta cells may cause early beta cell dysfunction and initiate autoimmunity. Mouse islets express lower levels of reactive oxygen species (ROS) clearing enzymes, such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase than several other tissues. It remains unclear if human beta cells show a similar deficiency during T1D or exhibit a higher degree of intrinsic resistance to oxidative stress. We compared islet cell distributions and determined graded intensities of glutathione peroxidase1 (GPX1), a key enzymatic mediator involved in detoxifying hydrogen peroxide, by applying combined immunohistochemistry for GPX1, insulin and glucagon, in pancreatic sections from new-onset T1D (group 1), non-diabetic autoantibody-negative (group 2), non-diabetic autoantibody-positive (group 3) and long-term diabetic (group 4) donors. Islets from all study groups demonstrated either uniform but graded staining intensities for GPX1 in almost all islet cells or strong staining in selective islet cells with weaker intensities in the remaining cells. GPX1 was present in selective glucagon cells and insulin cells, including in cells negative for both hormones, with stronger intensities in a higher percentage of glucagon than insulin cells. It was absent in a higher percentage of beta cells than glucagon cells independent of disease or autoantibody positivity. We conclude that a proportion of human beta cells and glucagon cells express GPX1 but show heterogeneity in its distribution and intensities, independent of disease or autoantibody status. Our studies highlight important differences in the expression of GPX1 in islet cell-types between mice and humans.