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Biology subjects

Takarada, T.

Publications and source records attributed to Takarada, T..

4 recordsLinked to original sources

The Role of Human-Specific lncRNA in Hyaline Cartilage Development

One of the distinctive characteristics of humans is their bipedalism. To achieve upright bipedal walking, the angles of the pelvis and femur have been altered. Although evolutionary hypotheses on the transition to bipedalism exist, the molecular mechanisms remain unclear. This study attempts to elucidate these mechanisms using a system for inducing hyaline cartilage-like tissue from human iPS cells via limb bud like mesenchymal cells. Focus was placed on non-coding RNAs, known for their potential in generating biological diversity. Bulk RNA sequencing was conducted to compare the expression and functions of human-specific long non-coding RNAs between limb bud like mesenchymal cells and induced hyaline cartilage-like tissue. The results indicated that human-specific lncRNAs, significantly upregulated in hyaline cartilage-like tissue, may regulate genes related to the extracellular matrix. These findings suggest the potential to develop regenerative cartilage tissue with enhanced ECM quality through controlling human-specific lncRNAs. Additionally, studying human-specific lncRNAs could elucidate mechanisms of diseases that are less common in other species but more prevalent in humans.

bioinformatics↗

Scaffold-free cryopreservable cartilage grafts obtained from hiPSC-derived chondroprogenitor cells for airway reconstruction with growth adaptability

Pediatric tracheal reconstruction remains a major clinical challenge because of limited graft availability and the need for growth-adaptive materials. Current approaches, such as costal cartilage grafting and use of scaffold-based constructs, often suffer from complications including graft resorption, donor site morbidity, and poor integration. Here, we present scaffold-free cartilage grafts (chondro-plates) derived from expandable limb-bud mesenchymal cells generated from human leukocyte antigen-homozygous human induced pluripotent stem cells. These grafts are cryopreservable and maintain their hyaline cartilage phenotype after a brief pre-culture. In both rat and rabbit tracheal defect models, chondro-plates supported robust cartilage regeneration, epithelial reconstitution, and neovascularization. Importantly, in a pediatric-like growing rat model, chondro-plates preserved luminal patency and structural integrity, outperforming autologous costal cartilage. This study demonstrates a clinically viable, off-the-shelf strategy for tracheal reconstruction using scalable, immunocompatible, and growth-adaptive cartilage grafts.

bioengineering↗

SGCRNA: Spectral Clustering-Guided Co-Expression Network Analysis Without Scale-Free Constraints for Multi-Omic Data

Weighted Gene Co-expression Network Analysis (WGCNA) is among the most widely employed methods in bioinformatics. WGCNA enables the identification of gene clusters (modules) exhibiting correlated expression patterns, the association of these modules with traits, and the exploration of candidate biomarker genes by focusing on hub genes within the modules. WGCNA has been successfully applied in diverse biological contexts. However, conventional algorithms manifest three principal limitations: the assumption of scale-free topology, the requirement for parameter tuning, and the neglect of regression line slopes. These limitations are addressed by SGCRNA. SGCRNA provides Julia functions for the analysis of co-expression networks derived from various types of biological data, such as gene expression data. The Julia packages and their source code are freely available at https://github.com/C37H41N2O6/SGCRNA.

bioinformatics↗

Modeling the human limb skeletal development using human pluripotent stem cell-derived skeletal assembloid

Despite recent advances in pluripotent stem cell-based approaches to induce skeletal cells, recapitulating human limb skeletal development in terms of structure and longitudinally oriented growth remains an unresolved challenge. Here, we report a method to differentiate human pluripotent stem cells into region-specific skeletal organoids harboring GDF5+PRG4+ interzone/articular chondrocyte progenitors (IZ/ACPs) and SP7+ growth plate chondrocytes (GPCs) via PRRX1+ limb-bud mesenchymal cells. Comparative analysis demonstrated marked similarities of IZ/ACP and GPC organoids to the human embryonic limb, and graft fate and regenerative capacity in vivo were further characterized. We also mimicked the limb skeletal developmental process in a spatially structured manner by vertically positioning two IZ/ACP organoids at both ends of a GPC organoid to generate a human skeletal assembloid. Notably, this human skeletal assembloid recapitulated endochondral ossification with longitudinal skeletal growth upon transplantation. In summary, our study provides a novel research platform for human limb skeletal development and disease.

bioengineering↗