Ribosome incorporation transdifferentiates chick primary cells and induces their proliferation by secreting growth factors

Previously, we reported that mammalian cells, specifically human dermal fibroblasts (HDFs), could be transdifferentiated by lactic acid bacteria (LAB). Later, we observed that HDFs incorporated LAB-derived ribosomes, forming the ribosome-induced cell clusters (RICs) and transdifferentiating into cells derived from all three germ layers. Based on this insight, we hypothesized that incorporating ribosomes into non-mammalian cells could reveal the universality of this mechanism and open the door to commercial applications. Our current study demonstrates that ribosome incorporation can transdifferentiate chick primary muscle-derived cells (CMCs) into adipocytes, osteoblasts, and chondrocytes. Furthermore, the culture medium supernatant from ribosome-incorporated CMCs was found to significantly enhance CMCs proliferation. RNA-seq analysis revealed that RICs-CMC exhibit increased expression of genes related to multi-lineage cell growth. In addition, we developed a novel technological shift in meat production—the "CulNet System"—which replicates organ interactions within mechanical systems for cell-cultured meat production. While significant efforts are still required to implement this technology in a cost-effective manner, we believe that combining the "CulNet System" with ribosome-incorporated multipotent cells that have prolonged culture capability could substantially improve the scalability and cost-effectiveness of cultured chicken meat production. This report highlights a promising approach for cell-culture-based meat production, offering a sustainable alternative to traditional methods. Type of manuscript: Article Title: Ribosome incorporation transdifferentiates chick primary cells and induces their proliferation by secreting growth factors Authors: Shota Inoue, Arif Istiaq, Anamika Datta, Mengxue Lu, Shintaro Nakayama, Kousei Takashi, Nobushige Nakajo, Shigehiko Tamura, Ikko Kawashima, Kunimasa Ohta Journal: Journal of Developmental Biology issue and page numbers: Volume 13, Issue 2,19 DOI: 10.3390/jdb13020019 Overall design: RNA-seq profiling of wildtype Chicken primary Muscle-derived Cells (CMCs) and ribosomes incoporated CMCs (RICs-CMC) at Day 14 in stem cell medium (ESGRO).

此前本团队已有报道称，哺乳动物细胞——具体为人真皮成纤维细胞（human dermal fibroblasts, HDFs）——可经乳酸菌（lactic acid bacteria, LAB）实现转分化。后续本团队观察到，HDFs可摄入乳酸菌来源的核糖体，形成核糖体诱导细胞簇（ribosome-induced cell clusters, RICs），并转分化为三胚层来源的各类细胞。基于上述发现，本团队提出假说：将核糖体引入非哺乳动物细胞，可揭示该机制的普适性，并为商业化应用开辟路径。本项最新研究证实，将核糖体引入鸡原代肌肉来源细胞（chick primary muscle-derived cells, CMCs），可使其转分化为脂肪细胞、成骨细胞及软骨细胞。此外，研究发现摄入核糖体的CMCs的培养上清液，可显著促进CMCs的增殖。RNA测序（RNA-seq）分析显示，RICs-CMC中与多谱系细胞生长相关的基因表达显著上调。此外，本团队开发了一种用于肉类生产的新型技术范式——“CulNet系统”，该系统可在机械系统中复现器官相互作用，用于细胞培养肉生产。尽管目前仍需开展大量工作以实现该技术的低成本落地，但本团队认为，将“CulNet系统”与具备长期培养能力的核糖体诱导多能细胞相结合，可大幅提升鸡肉细胞培养生产的可扩展性与成本效益。本研究报道了一种极具应用前景的细胞培养肉生产方案，可为传统生产方式提供可持续替代方案。

稿件类型：研究论文
论文标题：核糖体引入介导鸡原代细胞转分化并通过分泌生长因子促进其增殖
作者：井上翔太、阿里夫·伊斯蒂亚克、阿妮卡·达塔、陆梦雪、中山慎太郎、高泽浩介、中条伸茂、田村繁英、川岛一耕、太田国正
期刊：《发育生物学杂志》（Journal of Developmental Biology）
卷期与页码：第13卷，第2期，第19页；DOI：10.3390/jdb13020019
实验整体设计：对第14天处于干细胞培养基（ESGRO）中的野生型鸡原代肌肉来源细胞（CMCs）及核糖体摄入型CMCs（RICs-CMC）进行RNA-seq测序分析。