Intrinsically disordered region of Clr4/Suv39 regulates its enzymatic activity and ensures heterochromatin spreading.

Methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin, is catalyzed by Clr4/Suv39. Clr4/Suv39 contains two conserved domains-an N-terminal chromodomain and a C-terminal catalytic domain-connected by an intrinsically disordered region (IDR). Several mechanisms have been proposed to regulate Clr4/Suv39 activity, but how it is regulated under physiological conditions remains largely unknown.

Unraveling the regulative development and molecular mechanisms of identical sea urchin twins.

Since Hans Driesch's pioneering work in 1891, it has been known that animal embryos can develop into complete individuals even when divided. However, the developmental processes and molecular mechanisms enabling this self-organization remain poorly understood. In this study, we revisit Driesch's experiments by examining the development of isolated 2-cell stage blastomeres in the sea urchin, Hemicentrotus pulcherrimus.

Exploring Basement Membrane Dynamics through Cross-Scale Imaging, Manipulation, and Molecular Mapping.

The basement membrane (BM), a specialized extracellular matrix (ECM), provides structural support for epithelial, endothelial, and other parenchymal cells. Once considered a static scaffold, the BM is now recognized as a dynamic and complex nanostructure composed of a diversity of molecules that actively regulate cell behavior and tissue organization. Its molecular composition, assembly, and remodeling are precisely controlled in a tissue- and stage-specific manner, contributing to the regulation of local and global mechanical properties and biochemical signaling.

Similarities and differences in the intestinal actions of metformin and imeglimin.

Aims: Imeglimin is a novel antidiabetic drug that shares structural similarity with metformin. While the intestinal effects of metformin have attracted widespread attention, those of imeglimin remain underexplored.

Materials And Methods: C57BL/6J mice were treated with metformin or imeglimin for RNA sequencing of intestinal tissue.

Divergent evolutionary strategies pre-empt tissue collision in gastrulation.

Metazoan development proceeds through a series of morphogenetic events that sculpt body plans and organ structures. In the early embryo, these processes occur concurrently such that forces generated in neighbouring tissues can impose mechanical stresses on each other, potentially disrupting development and consequently decreasing fitness. How organisms evolved mechanisms to mitigate inter-tissue mechanical conflicts remains unclear.

Recellularization of decellularized vascular grafts via aligned seeding of endothelial cells derived from human iPS cells.

The development of decellularized vascular tissues for tissue engineering and vascular implants presents a promising approach to creating functional blood vessels. However, effective endothelialization with human endothelial cells remains challenging. This study examined the endothelialization of decellularized porcine aortas using human induced pluripotent stem (hiPS) cell-derived endothelial cells.

Single-cell transcriptomic reconstruction of the human hair cycle: Capturing the temporal dynamics of skin tissue remodeling.

The hair cycle is a valuable model for studying tissue remodeling processes in adult mammals. Time course single-cell transcriptomics offers a powerful approach for characterizing changes in cellular states and interactions; however, its application in human tissues remains challenging. Here, we performed single-cell RNA sequencing on 19 human skin tissues, each containing a single hair follicle.

Regulatory role of the N-terminal intrinsically disordered region of the DEAD-box RNA helicase DDX3X in selective RNA recognition.

DDX3X, a member of the DEAD-box RNA helicase family, plays a central role in the translational regulation of gene expression through its unwinding activity toward complex RNA structures in messenger RNAs (mRNAs). Although DDX3X is known to selectively stimulate the translation of a subset of genes, a specific sequence motif has not been identified; thus, the molecular mechanism underlying this selectivity remains elusive. Using solution nuclear magnetic resonance (NMR) spectroscopy, we demonstrate that the N-terminal intrinsically disordered region (IDR) of DDX3X plays a critical role in the binding and unwinding of structured RNAs.

Alteration of long- and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis.

Myeloid-biased hematopoiesis is a well-known age-related alteration. Several possibilities, including myeloid-biased hematopoietic stem cell (HSC) clones, may explain this. However, the precise mechanisms remain controversial.

SeeThrough: a rationally designed skull clearing technique for in vivo brain imaging.

Light scattering in the skull limits optical access to the brain. Here we present SeeThrough, a skull-clearing technique that enables simple, high-resolution, and minimally-invasive brain imaging without skull removal. Through systematic screening of over 1600 chemicals, we rationally developed a refractive index-matching solution that combines water- and organic solvent-based components, achieving both high clearing efficiency and biocompatibility.

Simultaneous in vitro expression of minimal 21 transfer RNAs by tRNA array method.

Transfer RNA (tRNA) plays a central role in translation. The simultaneous in vitro synthesis of minimal yet sufficient tRNA species (at least 21) poses a challenge for constructing a self-reproducible artificial cell. A key obstacle is the processing of the 5' and 3' ends, which requires a multi-step reaction in the natural cells.

Optogenetic actin network assembly on lipid bilayer uncovers the network density-dependent functions of actin-binding proteins.

The actin cytoskeleton forms a meshwork that drives cellular deformation. Network properties, determined by density and actin-binding proteins, are crucial, yet how density governs protein penetration and dynamics remains unclear. Here, we report an in vitro optogenetic system, named OptoVCA, enabling Arp2/3 complex-mediated actin assembly on lipid membranes.

Hidden Markov models reveal behavioral state dynamics in depth-related locomotion in mice.

Understanding how mice process and respond to visual depth cues is crucial for studying visual perception, yet traditional behavioral analyses often miss key aspects of this process, such as the dynamic transitions between behavioral states and the integration of multiple spatial cues that shape depth-related behaviors. Here we demonstrate that mouse responses to visual depth cues are more sophisticated than previously recognized, involving both direct avoidance behaviors and complex modulations of exploratory patterns. By combining a modified circular apparatus with Hidden Markov Model analysis, we reveal that mice transition between three distinct behavioral states-resting, exploring, and navigating-in response to visual depth cues.

Modeling of T cell-mediated autoimmune pituitary disease using human induced pluripotent stem cell-originated organoid.

Anti-pituitary-specific transcription factor (PIT)-1 hypophysitis is an autoimmune disease characterized by hormone secretion impairment from PIT-1-expressing pituitary cells, accompanied by malignancies with ectopic PIT-1 expression. Cytotoxic T cells (CTL) targeting PIT-1-positive cells have been implicated in disease development, yet direct evidence is lacking. As human leukocyte antigen (HLA)-matching is required for modeling T cell-mediated autoimmune diseases, we employ induced pluripotent stem cells (iPSC) to generate pituitary organoids harboring the patients' HLA haplotype and coculture the organoids with PIT-1-reactive CTLs isolated from the patients' peripheral blood mononuclear cells.

Structural analysis of a symbiotic system involving a Nanobdellati archaeon by cryo-electron tomography.

Nanobdellati (formerly DPANN) archaea are considered as primitive archaeal organisms that often live in symbiosis with archaeal hosts. In this study, we investigated the symbiotic mechanism between a Nanobdellati archaeon, Nanobdella aerobiophila strain MJ1, and its host archaeon Metallosphaera sedula strain MJ1HA, using cryo-electron tomography. In our tomographic observations, we identified a conical attachment organelle at the interface between MJ1 and MJ1HA during symbiosis.

Manipulating dietary protein and amino acids in the common marmoset Callithrix jacchus impacts circulating metabolites and FGF21 levels.

Restricting dietary protein intake has metabolic and physiological benefits for animals. Rodent studies have identified the involvement of a hormone, fibroblast growth factor 21 (FGF21), which is upregulated by sensing amino acid scarcity. However, to what extent this mechanism is conserved in primates remains elusive.

Migrating mesoderm cells self-organize into a dynamic meshwork structure during chick gastrulation.

Migration of cell populations is a fundamental process in morphogenesis and disease. The mechanisms of collective cell migration of epithelial cell populations have been well studied. It remains unclear, however, how the highly motile mesenchymal cells, which migrate extensively throughout the embryo, are connected with each other and coordinated as a collective.

Kif11-haploinsufficient oocytes reveal spatially differential requirements for chromosome biorientation.

Bipolar spindle assembly and chromosome biorientation are prerequisites for chromosome segregation during cell division. The kinesin motor KIF11 (also widely known as Eg5) drives spindle bipolarization by sliding antiparallel microtubules bidirectionally, elongating a spherical spindle into a bipolar-shaped structure in acentrosomal oocytes. During meiosis I, this process stretches homologous chromosome pairs, establishing chromosome biorientation at the spindle equator.

Three-dimensional analysis of intraepidermal nerve fibres and Langerhans cells in keloids with a focus on pruritus.

Keloids are intractable dermato-fibrotic lesions that progressively expands from the primary lesion to the surrounding normal areas. In this study, we investigated uncontrollable pruritus in keloids and the association between keloid symptoms and pruritus using three-dimensional immunofluorescence for the analysis of nerve fibres and Langerhans cells in the anterior chest and ear keloids, and the analysis of messenger-RNA expression of substance P as a pruritus mediator. Nerve fibres infiltrating the epidermis were numerous in the periphery of the anterior chest keloids, where pruritus was reported, with some extending into the granular layer.

Paracrine IGFBP3 spatially coordinates IGF signaling to induce myocardial regeneration in mice.

We hypothesized that the microenvironment of the regenerating neonatal mouse heart contains pro-mitotic factors. To identify non-cell-autonomous effectors of cardiomyocyte mitosis, we analyzed a transcriptomic screen of regenerating and non-regenerating hearts for differentially expressed secreted proteins. We identified IGFBP3 in this screen as a neonatal injury-associated secreted protein.

Role of Pcdh15 in the development of intrinsic polarity of inner ear hair cells.

In vertebrates, auditory information is transduced in the cochlea by mechanosensory hair cells (HC) through an eccentrically organised structure known as the hair bundle. This consists of a true cilium, known as the kinocilium, and modified microvilli, known as stereocilia. The hair bundle has a distinct structure with stereocilia organised in graded rows, with the longest abutting the kinocilium.

Linking neuron-axon-synapse architecture to white matter vasculature using high-resolution multimodal MRI in primate brain.

Blood vessels and axons align outside the brain due to shared growth factors. However, this neuron-axon-synapse and vessel relationship within the brain white matter remains unclear, primarily due to the technical challenges of charting the complex trajectories of fiber tracts and the dense network of arteries. Consequently, the organizational logic and neurometabolic factors shaping white matter vasculature remain poorly understood.

The distortion-push mechanism for the γ subunit rotation in F-ATPase.

F-ATPase comprises the stator ring consisting of αβ subunits and the rotor γ subunit. The γ subunit rotation mechanism has been extensively investigated by biochemical analyses, structural studies, single-molecule measurements, and computational studies. Recent cryoelectron microscopy (cryo-EM) structures of F-ATPase from the thermophilic bacterium PS3 (TF) provide us with further possibilities for a better understanding of the γ-rotation mechanisms.

A novel miniTurbo knock-in mouse reveals a protein interaction network of USP46 in the brain.

Uncovering protein interaction networks in vivo is essential for understanding physiological and pathological processes. Here, we report the generation of a novel knock-in mouse model expressing miniTurbo, a highly active biotin ligase, fused to the endogenous Usp46 gene. This model enables proximity-dependent biotinylation (BioID) of USP46-associated proteins in the brain.