Biology subjects

Hamaguchi, H.

Publications and source records attributed to Hamaguchi, H..

4 recordsLinked to original sources

bioRxiv2026

KK-LC-1 reveals evolutionary divergence in the regulation of sperm motility between humans and mice

CT83 (KK-LC-1) is a cancer-testis antigen originally identified in human lung cancer cells and has recently attracted attention as a potential target for cancer therapy. Although KK-LC-1 orthologs have been identified in up to 160 animal species, a murine homolog had not previously been identified, hindering in vivo analysis of its physiological function. In this study, we identified the mouse homolog of KK-LC-1 and performed a comparative analysis of its properties in humans and mice, together with an investigation of its biological function using gene knockout (KO) mice. The murine Kk-lc-1 gene is located on the X chromosome and, like its human counterpart, contains an N-terminal transmembrane domain. In both humans and mice, KK-LC-1 is expressed specifically in the testis and localizes to the head and tail regions of sperm. Analysis of Kk-lc-1-deficient mice revealed normal spermatogenesis, and both male and female KO mice were fertile. However, sperm from Kk-lc-1-deficient males exhibited reduced motility caused by decreased flexibility of the midpiece and failed to penetrate the oocyte zona pellucida in vitro. This defect was rescued by artificial insemination using epididymal sperm, suggesting that maternal factors in vivo may compensate for reduced sperm motility. Although impaired sperm motility during in vitro fertilization (IVF) was rescued by murine Kk-lc-1, functional rescue by human KK-LC-1 was not observed. These findings indicate that KK-LC-1 contributes to sperm motility but is not essential for fertility. Moreover, species-specific differences in KK-LC-1-mediated regulation of sperm motility suggest functional divergence during evolution. The role of KK-LC-1 in sperm motility should therefore be considered in the clinical development of cancer therapies targeting KK-LC-1.

developmental 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↗

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↗

bioRxiv2019

Single-cell information analysis reveals small intra- and large intercellular variations increase cellular information capacity

Cells transmit information about extracellular stimulation through signaling pathways to control cellular function. A signaling pathway can be regarded as a communication channel. In the analysis of channels of cell populations, intercellular variation is considered noise. However, intercellular variation enables individual cells to encode different information. Therefore, at the single-cell level, each cell can be regarded as an independent channel. Thus, we propose that responses of cells of the same type in tissues, such as the fibers in a skeletal muscle, should be regarded as a multiple-cell channel composed of single-cell channels, in which intercellular variation contains information. Here, we applied electrical pulses to individual myotubes from cultured C2C12 cells or dissociated skeletal muscle fibers and measured Ca2+ responses or contraction, respectively, to estimate information capacity in a biological system. For each muscle cell system, we found that a single-cell channel transmitted more information than did a cell-population channel, indicating that the cellular response is consistent with each cell (low intracellular variation) but different among individual cells (high intercellular variation). As cell number and thus the number of single-cell channels increased, a multiple-cell channel transmitted more information by incorporating the differences among individual cells. Thus, a tissue with small intracellular and large intercellular variations has the capacity to distinguish differences in stimulation intensity to precisely control physiological function.\n\nOne Sentence SummarySmall intracellular and large intercellular variations increase information transmission for precise control of tissue function.

systems biology↗