Cell and Tissue Research最新文献

Previous studies identified a rare cell type in the mouse tracheal epithelium with immunoreactivity to the microvillus protein villin (Vil1), which persisted in mice lacking tuft cells due to deletion of the transcription factor Pou2f3. This study aimed to clarify the identity of this ill-defined cell type. Ultrastructurally, all cells with tightly packed microvilli observed in the tracheal epithelium of Pou2f3^-/--mice contained basally located dense core vesicles, a characteristic feature of neuroendocrine cells (NEC). Accordingly, immunofluorescence double-labeling utilizing NEC markers revealed villin-labeling in two thirds of NEC in the trachea, a reporter mouse strain showed Cre recombinase activity driven by the Vil1 promoter in a subpopulation of tracheal NEC, and analysis of single cell RNA sequencing data revealed Vil1-mRNA expression by tracheal NEC. Notably, only a minimal fraction (≈1%) of bronchopulmonary NEC (solitary and clustered in neuroepithelial bodies) displayed villin-immunoreactivity, despite nearly half of them having a history of Vil1 promoter activity. Microvilli of tuft cells differed ultrastructurally from those of NEC, and the majority of tuft cells were immunoreactive to advillin (Avil), showed Avil promoter activity as indicated by a reporter mouse strain, and expressed Avil-mRNA in the sequencing data set. This study uncovers villin-expressing cells in the lower airways as a cell population hidden among NEC. Advillin, not villin, is identified as a marker for airway tuft cells. This should be considered in interpreting findings based on the use of villin as a marker or Cre-driver when investigating rare cells in the murine airways.

Connexin 43 (Cx43) is the principal connexin isoform expressed in the ventricular myocardium, where it is critically involved in the pathophysiology of cardiac ischemia-reperfusion injury. Its functions in this pathological condition span at least three different fronts. First, Cx43-mediated gap junctional channels contribute to the spread of cellular damage during reperfusion, allowing the transfer of sodium ions between injured and surviving cardiomyocytes. Further, under ischemic conditions, unapposed Cx43 hemichannels exacerbate injury by promoting calcium overload, metabolite losses, and membrane potential instability. Additionally, recent evidence suggest that mitochondrial Cx43 influences oxidative stress by modulating reactive oxygen species generation through the regulation of reverse electron transfer (RET) at the mitochondrial electron transport chain. These detrimental roles of Cx43 in acute myocardial ischemia-reperfusion injury, together with its previously described involvement in ischemic preconditioning, emphasize the dual functionality and importance of Cx43 in the context of acute myocardial infarction. The scope of this review is to summarize the current knowledge on the different mechanisms by which Cx43 promotes cell damage during myocardial infarction, with special emphasis on the regulation of RET.

Huntingtin-associated protein 1 (HAP1) is a core component of the stigmoid body (STB) and a neuroprotective interactor with the causative agents of several neurodegenerative diseases (NDs). The cholinergic system is often affected by NDs. Our previous studies suggest that cholinergic brainstem/spinal cord motoneurons are more vulnerable to neurodegeneration due to a lack of STB/HAP1 protectivity. The forebrain cholinergic nuclei are also major neurodegenerative/psychotic targets; however, the relationships of HAP1 with choline acetyltransferase (ChAT) have yet to be determined there. This study used western blotting and immunohistochemistry to evaluate the comparative distribution of HAP1 with ChAT and their immunohistochemical relationships in the adult mouse forebrain cholinergic nuclei. The results showed that HAP1-immunoreactive (ir) neurons were highly distributed in the basal forebrain cholinergic nuclei, including medial septal nucleus (MS), nucleus of vertical limb of the diagonal band of Broca (VDB), nucleus of horizontal limb of the diagonal band of Broca (HDB), and substantia innominata basal part (SIB). HAP1-ir neurons were sporadically scattered in the striatum. The significantly highest co-expression ratio of HAP1 with ChAT was observed in MS and VDB. In contrast, the ChAT-ir neurons never contained HAP1 in the caudate putamen of the striatum. These suggest that, due to having putative HAP1 protectivity, the cholinergic neurons in MS and VDB that are mainly projected to the hippocampal/parahippocampal regions might be protected to regulate social memory formation, emotion, and other psychological functions. Consequently, the lack of HAP1 protectivity might make cholinergic neurons in the striatum more prone to neurodegeneration in certain NDs.

The male reproductive system (MRS) of decapods in the genus Aegla remains poorly understood from both histological and ultrastructural perspectives. This study provides a comparative description of the anatomy, histology, and ultrastructure of the MRS in multiple Aegla species, with the aim of exploring their phylogenetic relationships with representatives of the superfamilies Lomisoidea and Chirostyloidea. Anatomically, the MRS of Aegla is located in the cephalothorax and consists of a bilateral structure. The testes are connected by a central commissure and independently open into each vas deferens. The vas deferens is a translucent tube subdivided into proximal, medial, and distal regions. Across all regions, the seminal fluid contains few free spermatozoa, and spermatophores are absent. This fluid comprises two types of secretion: type I (basophilic) and type II (strongly basophilic), both composed mainly of proteins and acidic polysaccharides, with interspecific variation in acidic polysaccharide content. Aegla spermatozoa exhibit a standard organization, organized into two hemispheres-cytoplasmic and nuclear-and possess an acrosome vesicle with two concentric layers. Comparatively, their ultrastructure closely resembles that of Lomis hirta, whereas members of Chirostyloidea lack similar features, indicating an evolutionary divergence. These findings contribute important insights into the evolutionary history of Anomura, highlighting the absence of spermatophores in Aegla-a condition typical of this infraorder-and underscoring the similarity in spermatozoa ultrastructure between Aegla and Lomis, likely reflecting a shared ancestral trait.

The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in lipid metabolism. More specifically, CYLD has been associated with lipid homeostasis in Drosophila melanogaster, and CYLD deficiency in mammals has been linked to dysregulation of lipid metabolism in the liver. Comprehensive tissue RNA expression analyses have revealed comparable levels of Cyld mRNA expression in the adipose tissue and liver, the organs that, together with skeletal muscle, primarily regulate lipid homeostasis. In the present study, the role of CYLD in mammalian adipose tissue homeostasis and function was investigated, utilizing a relevant conditional mouse model of CYLD inactivation that permits tissue-specific elimination of the catalytic domain of CYLD. Mutant mice displayed reduced weight-gain rate compared to controls when fed a normal or high-fat diet. Histological analysis of crown-like structures (CLS) indicated a reduced inflammatory response in the white adipose tissue of mutants. Our data collectively demonstrate that CYLD plays a pivotal role in regulating key metabolic parameters and modulating inflammatory responses within adipose tissue.

The posterior lobe (PL) of the vertebrate pituitary is richly vascularized with a dense network of fenestrated capillaries. In this study, we found that the expression of Aqp1, which encodes a plasma membrane-localized water channel protein, was significantly higher in endothelial fractions isolated from the rat PL than in those isolated from the anterior lobe (AL). Immunohistochemistry revealed aquaporin 1 (AQP1)-positive signals in fenestrated endothelial cells of the PL. Furthermore, immunoelectron microscopy demonstrated the presence of AQP1 signals on both the luminal and abluminal plasma membranes of these cells. AQP1 plays a pivotal role in facilitating water movement across the plasma membrane in response to changes in osmotic pressure on a cell. To investigate the effect of hyperosmolarity, we examined the expression levels of Aqp1 in the PL of water-deprived rats as well as in isolated endothelial cells of the PL cultured in a hyperosmotic medium supplemented with raffinose. Immunohistochemical analysis showed no changes in the proportion of AQP1-positive endothelial cells or in subcellular localization of AQP1 in cultured endothelial cells of the PL under hyperosmotic conditions. In contrast, analysis using quantitative real-time PCR revealed that hyperosmolar conditions significantly downregulated Aqp1 expression in cultured endothelial cells. These findings suggest that Aqp1expression in fenestrated capillaries in the PL is regulated by osmotic pressure of the interstitial fluid. Our results indicate that AQP1 is selectively expressed in fenestrated capillaries of the PL and plays a crucial role in maintaining water homeostasis in this region.

This study investigates the enteroepithelial stages of Toxoplasma gondii in the feline ileum using high resolution field emission scanning electron microscopy (FE-SEM) and serial block face scanning electron microscopy (SBF-SEM). By employing advanced imaging techniques, including creative sample processing methods, this research provides new insights into the development, distribution, and maturation of T. gondii within infected intestinal cells. Comparison with previous studies confirms earlier findings while offering enhanced resolution and three-dimensional models of the parasite's progression. SBF-SEM enabled the visualization of asexual forms of the parasite, from merozoites to multinucleated schizonts and rosettes, distributed along the intestinal villi. These observations suggest a tendency for merozoites to accumulate near the villus extrusion zone, where they are later released. Despite these advancements, the mechanisms of gamete fertilization and oocyst egress remain unresolved, highlighting key areas for future research.

Mesenchymal stem cells (MSCs) show promising therapeutic effects due to the proteins they secrete. However, MSCs from different sources exhibit only 60% similarity of proteins they secrete, suggesting that unique proteins may offer distinct therapeutic properties based on their origin. Amniotic fluid-derived MSCs (AFSCs) are promising for treating degenerative diseases and are unique in providing sufficient cells for fetal therapies. Nevertheless, their proteomic profiles remain largely undefined. This study investigated the proteomic profiles of bioactive molecules secreted by AFSCs (AFSC-se) using liquid chromatography and mass spectrometry, along with bioinformatics tools for protein function analysis. We identified over 2000 proteins in the AFSC-se that are involved in various mechanisms supporting organ development and function. The top three proteins identified were associated with organelle fusion, forebrain morphogenesis, and response to parathyroid hormone. Our findings indicate that AFSC-se has the ability to inhibit inflammation and apoptosis, which corresponds to 7.8% of the identified proteins involved in pathways related to these therapeutic effects. Furthermore, we discovered that 20% of identified proteins are associated with brain functions including synaptogenesis, neurogenesis, and neuroprotection. In conclusion, the proteomic profile of AFSC-se indicates its potential therapeutic effects. The significant presence of neuro-related proteins in AFSC-se suggests that AFSC-se may be a promising candidate for treating neurological diseases. Our work addresses existing knowledge gaps in this field.