Transcribed enhancer maps can reveal nuclear interactions underpinning each cell type and connect specific cell types to diseases. Using a 5′ single-cell RNA sequencing approach, we defined transcription start sites of enhancer RNAs and other classes of coding and noncoding RNAs in human CD4 + T cells, revealing cellular heterogeneity and differentiation trajectories. Integration of these datasets with single-cell chromatin profiles showed that active enhancers with bidirectional RNA transcription are highly cell type–specific and that disease heritability is strongly enriched in these enhancers. The resulting cell type–resolved multimodal atlas of bidirectionally transcribed enhancers, which we linked with promoters using fine-scale chromatin contact maps, enabled us to systematically interpret genetic variants associated with a range of immune-mediated diseases.
Cultivated meat can contribute to the global food supply; therefore, establishing efficient production processes is an urgent task to meet the growing demand for sustainable protein. Although cell culture technology has historically focused on suspension cells in the pharmaceutical and, subsequently, cultivated meat industries, the development of efficient processes for most adhesion-dependent cells has lagged, with limited examples reported to date. Therefore, this study used primary duck liver-derived adherent cells to develop and evaluate an integrated three-step meat production process involving pre-culture to select highly proliferative cells, packed-bed bioreactor expansion for mass production, and final processing, including packaging and heating. The established process allowed the efficient growth of selected cell populations while maintaining their proliferative characteristics. Moreover, the developed product met the microbiological and heavy metal safety criteria. Comprehensive compositional analysis (nutritional, amino acid, and fatty acid profiles) revealed that the product exhibited a protein profile distinct from that of conventional duck liver paste, along with a unique lower-fat signature. As productivity is dependent on cell doubling time, culture duration and monthly production were estimated for cells from various animal species. Overall, this study established a practical integrated production process for cultivated meat using adherent cells, providing a technological foundation for cellular agriculture applicable to diverse cell types and useful for future food supply diversification.
High production costs remain a major obstacle to the commercialization of cell-based foods, primarily because of the reliance on costly pharmaceutical-grade reagents and infrastructure. This study introduces a practical solution using a dual technical and regulatory approach. We developed iCoater, a ready-to-use food-grade coating agent for cell culture, using a process analogous to that used in food manufacturing. By applying terminal heat sterilization to food-grade gelatin, we developed a sterile and stable product without expensive filtration. In performance tests using primary duck liver-derived cells, iCoater showed efficacy in cell attachment and proliferation comparable to that of conventional coatings, maintaining quality for 12 months. Concurrently, we addressed the regulatory pathway for this novel product category under Japanese food legislation. We concluded that labeling the product as a "gelatin-processed food" is a realistic and transparent strategy. This integrated technological design and regulatory navigation approach provides a vital framework for future developments in cellular agriculture, paving the way for cost-effective and compliant production.