Biology subjects

Taguchi, M.

Publications and source records attributed to Taguchi, M..

8 recordsLinked to original sources

bioRxiv2026

An APP-centered molecular gateway integrates innate immunity and retinoic acid signaling to drive irreversible metamorphic commitment

The mechanisms by which environmental signals induce permanent developmental changes remain a fundamental biological problem. We investigated sea star metamorphosis, where microbial biofilms induce a total body plan reorganization. Using systems biology and functional assays, we identified a three-tiered signaling cascade: sensing, conversion, and execution. The immune adaptor MyD88 senses microbes, while MAPK proteins convert this signal into a retinoic acid developmental cue. An amyloid precursor protein (APP)-centered module acts as the irrevocable commitment gateway, stabilized by a positive feedback loop to ensure irreversibility. Remarkably, the genes driving this transition overlap with human pathways for Alzheimers disease and ADHD/Autism. By defining this ancient neuro-immune axis in an echinoderm adult body plan similar to the chordate head, our study establishes sea star metamorphosis as a model for understanding the evolutionary origins of human neurological disorders from the evolutionary developmental pathology perspective.

developmental biology↗

bioRxiv2025

Unique epigenomic signatures identify biologically significant subtypes of MDS and predict response to azacitidine

Myelodysplastic syndromes (MDS) are characterized by aberrant DNA methylation, and mutations in epigenetic modifiers are frequently found in these patients. Although DNA methyltransferase inhibitors (DNMTi) are used to treat MDS, response variability remains a challenge in the clinic, with limited predictive markers. Through comprehensive genomic, epigenomic, and transcriptomic analyses, we have gained valuable insights into the intricate interplay between genetic and epigenetic alterations in MDS. We describe aberrantly hyper and hypomethylated regions in MDS, extending beyond promoter regions and affecting long-distance regulatory elements. Using these aberrant DNA methylation patterns, we classified MDS patients into epigenetic subtypes correlated with known molecular drivers. This epigenetic classification includes a novel group of patients characterized only by their shared DNA methylation profile and lacking any genetic drivers. Furthermore, we identified a robust DNA methylation signature capable of distinguishing DNMTi responders from non-responders prior to receiving treatment. Leveraging these DMRs, we developed robust classifiers capable of predictive response to DNMTi by integrating DNA methylation, gene expression, mutations, and laboratory parameters. Our findings highlight the potential of epigenetic-based classifiers for personalized treatment approaches for MDS patients. Key PointsDNA methylation patterns define biologically meaningful MDS subtypes and uncover a new group lacking known mutations. A methylation-based signature at diagnosis predicts azacitidine response, supporting its use in guiding personalized MDS therapy.

cancer biology↗

bioRxiv2025

Combined stimuli of elasticity and microgrooves form aligned myotubes that characterize slow-twitch muscles

Skeletal muscles are classified into slow-twitch muscles composed primarily of type I and IIa fibers with high oxidative metabolism, and fast-twitch muscles composed of type IIx and IIb fibers with high glycolytic metabolism. Fiber-type shifts occur during development and aging; however, the stimuli that shift these types remain unclear. We analyzed the role of mechanical stimuli in myotube formation and shift to the characteristics of each fiber type using crosslinked gelatin gels with tunable elasticity (10-230 kPa) and microgrooves (3-50 {micro}m). C2C12 myotubes on 10 kPa gel increased the expression of marker genes for type I and IIa fibers (MYH7 and MYH2) and oxidative metabolism (GLUT4 and myoglobin) than those on stiffer gels. Upregulation of PGC-1 on soft gel induced a shift toward slow-twitch muscle genetic characteristics. Microgrooves (3-10 {micro}m) enhanced myoblast fusion and myotube orientation, without affecting the gene expressions characterizing fiber types. This study demonstrated an approach to create highly oriented slow-twitch muscle models by controlling the elasticity and microgrooves.

cell biology↗

bioRxiv2025

Type I collagen gels for assessing the combined effects of ligand concentration-dependent elasticity and fibril density on cells

Type I collagen (Col-I) is the most abundant fibrous protein in the extracellular matrix (ECM); its densification is involved in conditions including cancer, fibrosis, vascular diseases, and aging. Increased Col-I concentrations lead to increased ECM fibril density and stiffening; therefore, the effects of such changes in the microenvironment of cells require examination. Three types of Col-I gels were developed by introducing reagent-free radiation-induced crosslinking, while adjusting the distance between the Col-I monomers or fibrils. The adhesion area of HeLa human cervical cancer epithelial cells, human induced pluripotent stem (hiPS) cells, and 3T3-Swiss albino mouse embryonic fibroblasts, tended to decrease with increasing fibril density when the ligand concentration-dependent elasticity (C-E) was constant. In the absence of fibrils, the adhesion area of HeLa and 3T3-swiss cells increased with increasing C-E, whereas hiPS cells clustered regardless of C-E. When C-E and the fibril density increased simultaneously, the adhesion area of HeLa and 3T3-swiss cells remained unchanged due to the two opposing effects. Our results highlight the importance of evaluating the combined effects of the compositional, mechanical, and topographical cues of Col-I on cells. The developed Col-I gels will contribute to elucidating the role of Col-I in development, differentiation, regeneration, disease, and aging. HighlightsO_LICol-I concentration-dependent elasticity (C-E) and fibril density were separated. C_LIO_LIAdhesion areas of cells decreased with increasing fibril density at constant C-E. C_LIO_LIAdhesion areas of cells increased with increasing C-E in absence of Col-I fibrils. C_LIO_LIAdhesion areas remained unchanged when both C-E and fibril density increased. C_LIO_LIStructural, mechanical and topographical cues work in combination to affect cells. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/642521v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@11b5779org.highwire.dtl.DTLVardef@bd1b5org.highwire.dtl.DTLVardef@1f4cf6eorg.highwire.dtl.DTLVardef@15e7f5c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Spatiotemporal temperature control by holographic heating microscopy unveils cellular thermosensitive calcium signaling

Optical microheating technologies have revealed how biological systems sense heating and cooling at the microscopic scale. Sensing is based on thermosensitive biochemical reactions that frequently engage membrane proteins, Ca2+ channels, and pumps to convert sensing information as the Ca2+ signaling in cells. These findings highlight the feasibility of thermally manipulating intracellular Ca2+ signaling. However, how the thermosensitive Ca2+ signaling would behave, particularly in multicellular systems, remains elusive. In this study, to extend the ability of the spatiotemporal temperature control by optical microheating technologies, we propose holographic heating microscopy. Water-absorbable infrared (IR) laser light is modulated by a reflective liquid crystal on a silicon spatial light modulator (LCOS-SLM). A computer-generated hologram displayed on the LCOS-SLM modulates the spatial phase pattern of the IR laser light to generate predesigned temperature gradients at the microscope focal plane. The holographic heating microscopy visualizes how thermosensitive Ca2+ signaling is generated and propagated in MDCK cells, rat hippocampal neurons, and rat neonatal cardiomyocytes. Moreover, the optical control of the temporal temperature gradient reveals the cooling-rate dependency of Ca2+ signaling in HeLa cells. These findings demonstrate the extended ability of holographic heating microscopy in investigating cellular thermosensitivities and thermally manipulating cellular functions.

biophysics↗

bioRxiv2024

BLOC: buildable and linkable organ on a chip

Microphysiological systems (MPSs) are attractive alternatives to animal experiments in physiology, pathophysiology, and drug development. However, conventional MPSs are designed for specific applications and have low versatility and scalability. Here, we developed a "Buildable and Linkable Organ on a Chip" (BLOC) to construct diverse MPSs. The Culture, Control, and Analysis BLOCs were standardized to the same size and linked using inlet/outlet joints for perfusion. Radiation-induced chemical reactions were used to suppress the adsorption and absorption of small hydrophobic molecules by BLOCs composed of polydimethylsiloxane. BLOCs for 2D/3D culture could also encapsulate radiation-crosslinked protein hydrogels with designed stiffness and microtopography to mimic the microenvironment in vivo. A perfusion device connecting Culture BLOCs was designed for a toxicity assay mimicking the systemic circulation using six types of organoids. An automatic enzyme-linked immunosorbent assay device connecting Culture, Control, and Analysis BLOCs detected proteins released from organoids. BLOCs, which users can freely configure to suit their needs, is expected to become powerful tools in basic research and preclinical trials using MPSs.

bioengineering↗

bioRxiv2024

JMJD3 mediated senescence is required to overcome stress induced hematopoietic defects.

Cellular senescence in stem cells compromises regenerative capacity, promotes chronic inflammation, and is implicated in aging. Hematopoietic stem and progenitor cells (HSPCs) are responsible for producing mature blood cells, however, how cellular senescence influences their function is largely unknown. Here, we show that JMJD3, a histone demethylase, activates cellular senescence via p16Ink4a upregulation in competition with Polycomb group proteins, and reprograms HSPC integrity to overcome hematopoietic defects induced by replicative and oncogenic stresses. JMJD3 deficiency impaired stem cell potential, proper cell cycle regulation, and WNT pathway activation in HSPCs under stress conditions. These impaired phenotypes were rescued through exogenous and retroviral introduction of p16Ink4a. This JMJD3-p16INK4a axis in hematopoiesis is age-dependent and is distinct from cellular senescence. Treatment with a JMJD3 selective inhibitor attenuated leukemic potential during cellular senescence. Taken together, these results demonstrate that JMJD3-p16INK4a mediates cellular senescence and plays critical roles in the functional integrity of HSPCs under stress conditions, suggesting a new link for aging and anti-cancer therapies.

cell biology↗

bioRxiv2019

Elasticity and Topography-Controlled Collagen Hydrogels Mimicking Native Cellular Milieus

Accumulating evidence demonstrates that the elasticity and topography of a cell culture substrate influence cell behavior, in addition to its chemical composition. However, cellular responses to in vivo extracellular matrix (ECM), a hydrogel of proteins (mainly collagen) with various elasticity and a nanometer-to micrometer-scale topography, remain to be elucidated owing to a lack of substrate that provides such complex cues. This study introduces novel collagen hydrogels that can combine, for the first time, elastic, topographic, and compositional cues that recapitulate native ECM. A simple and reagent-free method based on radiation crosslinking alters ECM-derived collagen solutions into hydrogels with a well-defined and tunable elastic modulus covering the broad range of soft tissues (1-236 kPa) and microtopographies while ensuring intrinsic biological functionality of collagen. These collagen hydrogels enabled investigating cell responses to soft topographic cues such as those encountered in vivo, revealing that topography overrides the elasticity and structurally constrains cell morphology by controlling actin cytoskeleton organization. The collagen hydrogels not only reduce in vivo and in vitro behavioral disparity of cells by mimicking native ECM but also facilitate the design of artificial ECM to control cell function and fate in tissue engineering and regenerative medicine.

bioengineering↗