Biology subjects

Kagaya, K.

Publications and source records attributed to Kagaya, K..

5 recordsLinked to original sources

bioRxiv2025

Niche-targeted therapy via YAP/TAZ activation enhances hematopoietic regeneration

The distinctive milieu of the bone marrow (BM), known as the BM niche, supports hematopoietic stem cells (HSCs) and serves as a foundation for hematopoietic regeneration. Myeloablative stress disrupts not only hematopoietic stem and progenitor cells but also essential BM niche components, including endothelial cells (ECs) and mesenchymal stromal cells (MSCs); disruption of the latter impairs efficient hematopoietic recovery. However, therapeutic strategies targeting niche restoration remain largely underdeveloped. Here, we demonstrate that the Hippo pathway effectors YAP/TAZ are critical for enabling ECs and MSCs to respond to BM injury, and that YAP/TAZ activation accelerates BM niche recovery, thereby promoting hematopoietic regeneration. We found that YAP/TAZ are rapidly activated in both MSCs and ECs following myeloablative stress, maintaining MSC multipotency and orchestrating vascular remodeling. Mechanistically, YAP/TAZ function as transcriptional hubs in MSCs, regulating key transcriptional factors such as Ebf1 and Ebf3. This regulation preserves MSC identity by preventing osteogenic and fibrogenic differentiation while promoting the expression of hematopoietic factors such as Cxcl12 and angiogenic factors. In parallel, YAP/TAZ signaling in ECs facilitates pro-angiogenic responses and drives sinusoidal vessel remodeling after injury. These YAP/TAZ-mediated niche responses are essential for HSC retention and hematopoietic regeneration following diverse myelosuppressive therapies. Notably, pharmacological activation of YAP/TAZ enhances BM niche reorganization and augments hematopoietic regeneration following myeloablative therapies. These findings establish YAP/TAZ as central regulators of BM niche resilience, providing a rationale for niche-targeted therapeutic strategies to enhance hematopoietic regeneration. Key points{blacksquare} YAP/TAZ enable BM niche cells to sense injury and restore their structure and function, thereby promoting hematopoietic regeneration. {blacksquare}Pharmacological activation of YAP/TAZ enhances BM niche resilience and accelerates hematopoietic recovery after myelosuppressive therapies.

cell biology↗

bioRxiv2022

Embodied Latch Mechanism of the Mandible to Power at an Ultrahigh Speed in the Trap-jaw Ants Odontomachus kuroiwae

Rapid movements of limbs and appendages, faster than those produced by simple muscle contraction alone, are generated through mechanical networks consisting of springs and latches. The latch plays a central role in these spring-loaded mechanisms, but the structural details of the latch are not always known. The mandibles of the trapjaw ant Odontomachus kuroiwae closes the mandible extremely quickly to capture prey or to perform mandible-powered defensive jumps to avoid potential threats. The jump is mediated by a mechanical spring and latch system embodied in the mandible. An ant can strike the tip of the mandible onto the surface of an obstacle (prey, predator, or ground) in order to bounce its body away from potential threats. The angular velocity of the closing mandible was 2.3x104 rad/s. Latching of the joint is a key mechanism to aid the storage of energy required to power the ballistic movements of the mandibles. We have identified the fine structure of two latch systems on the mandible forming a balljoint using an X-ray micro-computational tomography system (X-ray micro-CT) and X-ray live imaging with a synchrotron. Here we describe the surface of the inner section of the socket and a projection on the lip of the ball. The X-ray live imaging and movements of the 3D model show that the ball with a detent ridge slipped into a socket and over the socket ridge before snapping back at the groove edge. Our results give insight into the complex spring-latch systems that underpin ultra-fast movements in biological systems.

animal behavior and cognition↗

bioRxiv2019

Generalized locomotion of brittle stars with an arbitrary number of arms

Typical brittle stars have five radially symmetrical arms, which coordinate to move their body in a certain direction. However, some species of them show individual difference in the number of arms. We found this trait unique since intact legged animals each own a fixed number of limbs in general. How does a single species manage such different numbers of motile organs to realize adaptive locomotion? We here described four-, five-, six-, and seven-armed locomotion with the aim to generalize a common rule which is flexible with arm numbers in brittle stars. We mechanically stimulated an arm in Ophiactis brachyaspis to analyze escape direction and arm movements. Gathering quantitative indices and employing Bayesian statistical modeling, we figured out an average locomotion: regardless of the total number of arms, a front position emerges at one of the second neighboring arms to a mechanically stimulated arm, while side arms adjacent to the front synchronously work as left and right rowers. We suggest a model where some afferent signal runs either clockwise or anticlockwise along the nerve ring while linearly counting how many arms it passes. This idea would explain how left and right emerges in a radially symmetrical body via a decentralized system.

animal behavior and cognition↗

bioRxiv2019

A Single Defined Sister Chromatid Fusion Destabilizes Cell Cycle through Micronuclei Formation

Chromosome fusion is deleterious among oncogenic chromosome rearrangements, and has been proposed to cause multiple tumor-driving abnormalities. Conventional methodologies, however, lack the strictness of the experimental controls on the fusion such as the exact timing, the number and the types of fusion in a given cell. Here, we developed a human cell-based sister chromatid fusion visualization system (FuVis), in which a single defined sister chromatid fusion is induced by CRISPR/Cas9 concomitantly with mCitrine expression. Fused chromosome developed numerical and structural abnormalities, including chromosome fragmentation, an indicative of eventual chromothripsis. Live cell imaging and hierarchical Bayesian modeling indicated that micronucleus (MN) is generated in the first few cell cycle, and that cells with MN tend to possess cell cycle abnormalities. These results demonstrate that, although most cells can tolerate a single fusion, even a single sister chromatid fusion destabilizes cell cycle through MN formation.

cell biology↗

bioRxiv2018

Customizing material into embodied cap by sponge crab

Animal personality is considered to be developed through complex interactions of an individual with its surrounding environment. How can we quantify the personality of an individual? Quantifying intra- and inter-individual variability of behavior, or individual behavioral type, appears to be a prerequisite in the study of animal personality. We propose a statistical method from a predictive point of view to measure the appropriateness of our assumption of individual behavior in repeatedly measured behavioral data from several individuals. For a model case, we studied the sponge crab Lauridromia dehaani known to make and carry a cap from a natural sponge for camouflage. Because a cap is most likely to be rebuilt and replaced repeatedly, we hypothesized that each individual crab would grow a unique behavioral type and it would be observed under an experimentally controlled environmental condition. To test the hypothesis, we conducted behavioral experiments and employed a new Bayesian model-based comparison method to examine whether crabs have individual behavioral types in the cap making behavior. Crabs were given behavioral choices by using artificial sponges of three different sizes. We modeled the choice of sponges, size of the trimmed part of a cap, size of the cavity of a cap, and the latency to produce a cap, as random variables in 26 models, including hierarchical models specifying the behavioral types. In addition, we calculated the marginal-level widely applicable information criterion (mWAIC) values for hierarchical models to evaluate and compared them with the non-hierarchical models from the predictive point of view. As a result, the crabs of less than about 9 cm in size were found to make caps from the sponges. The body size explained the behavioral variables namely, choice, trimmed cap characteristics, and cavity size, but not latency. Furthermore, we captured the behavioral type as a probabilistic distribution structure of the behavioral data by comparing WAIC. Our statistical approach is not limited to behavioral data but is also applicable to physiological or morphological data when examining whether some group structure exists behind fluctuating empirical data.

animal behavior and cognition↗