Biology subjects

Uchiyama, R.

Publications and source records attributed to Uchiyama, R..

3 recordsLinked to original sources

bioRxiv2026

Enhancing the hyaline cartilage regenerative potential of induced pluripotent stem cell-derived chondrocyte cell sheets

Introduction Autologous and allogeneic chondrocyte cell sheet transplantation has shown safety and potential efficacy for cartilage defects associated with knee osteoarthritis. Although polydactyly-derived chondrocyte (PDC) cell sheets have been used clinically for allogeneic transplantation, a scalable and reliable alternative cell source is needed. This study aimed to establish a proof-of-concept protocol for generating chondrocyte cell sheets from clinical-grade human induced pluripotent stem cells (iPS cells). Methods Cartilaginous tissue was generated from human iPS cells, and isolated chondrocytes were used to fabricate iPS cell-derived chondrocyte sheets. In Phase 1, sheets were produced in high-serum medium under normoxic, hypoxic, or hypoxic/high-seeding-density conditions and compared with PDC sheets using a three-dimensional in vitro model and xenogeneic orthotopic transplantation in an immunodeficient rat model. In Phase 2, sheets were produced in low-serum medium under hypoxic/high-seeding-density conditions and evaluated for cartilage-related gene expression, secreted factors, cell surface marker expression, and in vivo cartilage repair. Results In Phase 1, hypoxic/high-seeding-density culture enhanced in vitro chondrogenic properties. However, after transplantation, iPS cell-derived chondrocyte sheets formed fibrotic repair tissue, whereas PDC sheets generated hyaline-like cartilage. In Phase 2, low-serum culture increased expression of cartilage-related genes, including collagen type II alpha 1 (COL2A1) and SRY-box transcription factor 9 (SOX9), enhanced secretion of transforming growth factor beta 1 and melanoma inhibitory activity, and upregulated CD9, CD26, CD56, CD201, CD227, and GD2. Low-serum iPS cell-derived chondrocyte sheets regenerated hyaline cartilage at 4 weeks, and the repair tissue was maintained at 12 weeks without bone formation. Conclusions A robust fabrication protocol enabled human iPS cell-derived chondrocyte sheets to regenerate hyaline-like cartilage in vivo. These findings support their potential as a scalable cell source for clinical cartilage repair.

bioengineering↗

bioRxiv2021

Vision-to-value transformations in artificial network and human brains

Humans and now computers can derive subjective valuations from sensory events although such transformation process is essentially unknown. In this study, we elucidated unknown neural mechanisms by comparing convolutional neural networks (CNNs) to their corresponding representations in humans. Specifically, we optimized CNNs to predict aesthetic valuations of paintings and examined the relationship between the CNN representations and brain activity via multivoxel pattern analysis. Primary visual cortex and higher association cortex activities were similar to computations in shallow CNN layers and deeper layers, respectively. The vision-to-value transformation is hence proved to be a hierarchical process which is consistent with the principal gradient that connects unimodal to transmodal brain regions (i.e. default mode network). The activity of the frontal and parietal cortices was approximated by goal-driven CNN. Consequently, representations of the hidden layers of CNNs can be understood and visualized by their correspondence with brain activity-facilitating parallels between artificial intelligence and neuroscience.

neuroscience↗

bioRxiv2020

Cultural Evolution of Genetic Heritability

Behavioral genetics and cultural evolution have both revolutionized our understanding of human behavior, but largely independently of each other. Here we reconcile these two fields using a dual inheritance approach, which offers a more nuanced understanding of the interaction between genes and culture, and a resolution to several long-standing puzzles. For example, by neglecting how human environments are extensively shaped by cultural dynamics, behavioral genetic approaches systematically inflate heritability estimates and thereby overestimate the genetic basis of human behavior. A WEIRD (Western, educated, industrialized, rich, democratic) gene problem obscures this inflation. Considering both genetic and cultural evolutionary forces, heritability scores become less a property of a trait and more a moving target that responds to cultural and social changes. Ignoring cultural evolutionary forces leads to an over-simplified model of gene-to-phenotype causality. When cumulative culture functionally overlaps with genes, genetic effects become masked, or even reversed, and the causal effect of an identified gene is confounded with features of the cultural environment, specific to a particular society at a particular time. This framework helps explain why it is easier to discover genes for deficiencies than genes for abilities. With this framework, we predict the ways in which heritability should differ between societies, between socioeconomic levels within some societies but not others, and over the life course. An integrated cultural evolutionary behavioral genetics cuts through the nature-nurture debate and elucidates controversial topics such as general intelligence.

genetics↗