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Konishi, S.

Publications and source records attributed to Konishi, S..

8 recordsLinked to original sources
bioRxiv2026

Differential associations of insulin resistance with anterior hippocampal volume in mild cognitive impairment and Alzheimer's disease

Insulin resistance is increasingly recognized as a metabolic factor associated with Alzheimers disease (AD); however, its relevance to hippocampal structural changes--a key pathological feature of AD--across disease stages is not fully understood. To address this issue, we investigated the relationship between insulin resistance, hippocampal gray matter volume, and cognitive performance using data from the Alzheimers Disease Neuroimaging Initiative (ADNI), a large-scale neuroimaging dataset. Insulin resistance was assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and its relationship with brain structure and cognitive performance was evaluated across diagnostic groups. In the mild cognitive impairment (MCI) group, higher insulin resistance was associated with larger anterior hippocampal gray matter volume, whereas in the AD group this association was reversed in direction. Furthermore, in the MCI group, anterior hippocampal gray matter volume was also positively associated with higher Mini-Mental State Examination (MMSE) scores, and an exploratory mediation analysis suggested a significant indirect association linking HOMA-IR, anterior hippocampal volume, and cognitive performance through anterior hippocampal volume. These findings suggest that the relationship between insulin resistance and AD-related brain changes differs across diagnostic groups, highlighting the importance of considering metabolic alterations in relation to disease status.

neuroscience↗
bioRxiv2026

Human club cells derived from pluripotent stem cells reveal new insights into epithelial lineage plasticity through structural and functional validation

Airway epithelial homeostasis relies on multiple specialized cell types, with club cells playing central roles in maintaining epithelial integrity and regulating inflammation. Environmental insults such as allergens, viral infections, or pollutants preferentially damage club cells, impairing epithelial repair and contributing to pulmonary diseases. However, the functional properties of club cells remain incompletely defined, and tractable human models are lacking. Herein, we establish a robust platform to differentiate human pluripotent stem cells (hPSCs) into club cells exhibiting their hallmark secretory features, appropriate epithelial organization, and functional properties. Single-cell transcriptomic analyses and lineage trajectory inference revealed unexpected epithelial plasticity: hPSC-derived club cells give rise to multiciliated epithelial cells through a deuterosomal intermediate--a previously uncharacterized trajectory. Additionally, a distinct club cell subset exhibited transcriptional features indicative of neuroendocrine and goblet cell differentiation potential. This study uncovers club cell plasticity and establishes a hPSC-based platform for studying airway development, regeneration and disease modeling.

cell biology↗
bioRxiv2026

In vivo xenogenic reconstitution of human alveolar epithelial architecture and function

An urgent need exists for lung models that accurately replicate human physiological profiles. We developed a chimeric mouse model enabling targeted ablation of alveolar type 2 (AT2) cells and lung macrophages, creating niches for endoscopically transplanted human induced pluripotent stem cell (hiPSC)-derived lung progenitors (hLPs). These engrafted cells were retained for 24 weeks, demonstrating self-renewal and differentiation potential, surfactant protein secretion, and maintaining alveolar phosphate homeostasis, suggesting their maturation into AT2 cells. Furthermore, transplantation of hLPs derived from disease-specific hiPSCs recapitulated the phenotype of pulmonary alveolar microlithiasis. The architecture, function, and metabolism of human alveolar epithelium were accurately replicated in vivo. This model has the potential to link experimental models and first-in-human studies, facilitating the development of novel therapies for intractable lung diseases.

developmental biology↗
bioRxiv2024

Development of a flexible 3D printed TPU-PVC microfluidic devices for organ-on-a-chip applications

The development of cost-effective, flexible, and scalable microfluidic devices is crucial for advancing organ-on-a-chip (OoC) technology for drug discovery and disease modeling applications. In this study, we present a novel 3D-printed flexible microfluidic device (3D- FlexTPU-MFD) fabricated through a one-step fused deposition modeling (FDM) process using thermoplastic polyurethane (TPU) as the printing filament and polyvinyl chloride (PVC) as the bonding substrate. The devices compatibility was evaluated with various cell types, including human primary myoblasts, human primary endothelial cells (HUVEC), and human iPSC- derived optic vesicle (OV) organoids. Myoblasts cultured within the device exhibited high viability, successful differentiation, and the formation of aligned myotube bundles, outperforming conventional well-plate cultures. Additionally, iPSC-derived OV organoids- maintained viability, displayed neurite outgrowth, and sustained expression of the eye marker PAX6. These results demonstrate that the 3D-FlexTPU-MFD effectively supports cell growth, differentiation, and alignment, making it a promising platform for tissue modeling and OoC applications in future.

bioengineering↗
bioRxiv2024

Development and characterization of bioinks for 3D bioprinting of in vitro skeletal muscle constructs

The use of 3D bioprinting to construct in vitro skeletal muscle models presents a promising approach; however, selecting an optimal bioink remains a common challenge. This study focuses on the development and characterization of bioinks for extrusion-based 3D bioprinting, specifically targeting the creation of accurate skeletal muscle models. By exploring various compositions of alginate, gelatin, fibrinogen, and nanofiber cellulose, we evaluate these formulations based on printability and their support for the growth and differentiation of C2C12 myoblast cells. While alginate provided a strong, stable matrix for printing scaffolds embedded with C2C12 cells, it did not effectively promote cell growth and differentiation. The addition of fibrinogen to alginate enhanced cell growth and differentiation but was limited mainly to the scaffold surfaces, even with the inclusion of gelatin as a sacrificial ink. Notably, replacing alginate with nanofiber cellulose (NFC) alongside fibrinogen significantly improved cell growth and differentiation, leading to the formation of mature myotubes. Cell distribution was observed both inside and on the surfaces of the scaffolds, indicating effective spatial cell distribution. Furthermore, the scaffolds were tailored to form skeletal muscle bundles anchored between PDMS pillars for contractility testing. Upon exposure to electrical stimulation, the cells displayed measurable displacement, demonstrating contractile function. These findings offer valuable insights into optimizing bioink formulations that promote myoblast growth and differentiation into skeletal muscle in vitro, with potential applications in future neuromuscular disease modeling.

bioengineering↗
bioRxiv2023

Diurnal variation of brain activity in the human suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However, the circadian activity of the human SCN has remained elusive. In this study, to reveal the diurnal variation of the SCN activity in humans, the SCN was localized, and its activity was investigated using perfusion imaging. We scanned each participant four times a day, every six hours, and higher activity was observed at noon while lower activity was recorded in the early morning. The SCN activity was then measured every thirty minutes for six hours from midnight to dawn and showed a decreasing trend and was comparable with the rodent SCN activity after switching off the lights. These results suggest that the diurnal variation of the human SCN follows the zeitgeber cycles of mammals and is modulated by physical lights rather than the local time.

neuroscience↗
bioRxiv2022

Parent-Child Autonomic Synchrony During Vicarious Extinction Learning in Pediatric PTSD

Children learn about threat and safety in their environment in part from their caregivers, a process which may be disrupted in child psychopathology. This transmission may be seen through biological measures like peripheral nervous system outputs such as skin conductance (SCR). Fear learning deficits have been observed in fear-related disorders like PTSD but have received little study in terms of parent-child learning transmission. We used a vicarious fear extinction paradigm to examine whether biological synchrony (SCR and heart rate variability [HRV]) is a potential mechanism by which children learn safety cues from their parents. In this pilot study, 16 dyads (PTSD n=11, typically developing [TD] n=5) underwent a vicarious fear extinction paradigm. We used cross-recurrence quantification analysis (CRQA) to assess SCR and HRV synchrony between parent-child dyads. We then used a linear model to examine group differences between PTSD dyads and TD dyads. For SCR, a significant group difference (p=.037) indicated that TD dyads had higher SCR synchrony compared to PTSD dyads. For HRV, there were no group differences between PTSD and TD dyads (p=.325). In exploratory analyses, increased synchrony was related to an overall decreased autonomic reactivity during recall of fear (p=0.032). These results suggest that SCR synchrony, but not HRV, may be a potential mechanism that allows for fear and safety learning in youth. While these data are preliminary, they provide novel insights on how disruptions in vicarious extinction learning may contribute to fear-related disorders in youth. Furthermore, this study suggests novel approaches to studying dyadic trauma-focused therapies which critically rely on parental coaching to model appropriate fear responses to help their child to recover from trauma. Significance StatementThis study provides evidence that biological synchrony is a potential mechanism through which youth learn threat and safety cues through their parents. We found that youth with PTSD have lower synchrony with their caregiver, and that synchrony was related to decreased overall autonomic reactivity, suggesting that synchrony may be indicative of overall safety learning. Further, decreased synchrony during fear extinction may potentially underlie the etiology of fear related disorders such as PTSD. These novel approaches may improve our understanding of dyadic trauma-focused therapies which critically rely on parental coaching to model appropriate fear responses to help their child to recover from trauma.

neuroscience↗