以往大多数与肢体相关的类器官模型仅关注中胚层，忽略了AER和其他皮肤细胞（表层外胚层）在肢体 形成中的指导作用。此次为制造"布多伊德"，研究团队从小鼠胚胎干细胞中培养出混合细胞群，这些细 胞自然形成了类似AER、表层外胚层和中胚层细胞，基本涵盖了发育中肢体的所有主要细胞类型。当这 些细胞被聚合时，它们能够自我组织成三维结构。团队随后利用该系统研究AER细胞是如何引导组织形 成的。 "布多伊德"提供了一种全新的实用系统，使人们能够探索胚胎发育中难以深入研究的领域，例如细胞如 何协调行为、早期结构如何发育以及软骨如何形成。其应用不仅限于基础研究，未来还将涉及先天性疾 病建模、测试可能损害肢体发育的化学物质，甚至促进再生医学的应用。 瑞士洛桑联邦理工学院一组团队利用干细胞制造了全新三维类器官——"布多伊德"。这种类器官展现了 发育中肢体的多个关键特征，包括对称破缺（塑造肢体的第一步）和早期软骨形成。该研究发表在最新 一期《科学进展》杂志上。 在胚胎早期发育阶段，身体器官的构建依赖于不同细胞类型之间化学信号的交换。以肢体发育为例，肢 体表面一层被称为"顶端外胚层脊"（AER）的薄层皮肤细胞会发出信号，引导下方细胞群生 ...

Core Viewpoint - The research presents a novel method for constructing embryonic models using chemically induced embryonic founder cells (EFC), which allows for a more efficient and accurate simulation of mouse embryogenesis and organogenesis [2][3][6]. Group 1: Research Methodology - The study utilized small molecules (CHIR-99021, E-616452, Lif, AM580) to induce mouse embryonic stem cells into 8-16 cell stage embryonic founder cells (EFC) [6]. - EFC cells can determine all lineages of blastocysts both in vivo and in vitro, enabling the construction of a complete embryonic model [6][9]. - The model accurately replicates the developmental process starting from organ formation, including the formation of three germ layers and early organ structures [6][9]. Group 2: Research Highlights - The system using EFCs allows for direct, rapid, efficient, and accurate construction of in vitro embryonic development models [8]. - Induced EFCs (iEFC) can generate a scalable and faithful embryonic model (iEFC-EM) that reproduces mouse embryonic development up to the organ formation stage [9]. - The model demonstrates the transformation of epithelial cells to mesenchymal cells during gastrulation, leading to the development of various early organ precursors and structures [6][9].

Core Insights - The article discusses the significant role of mitochondria in mammalian development and introduces a new method for enforced mitophagy that allows for the reduction or complete removal of mitochondria, revealing their influence on pluripotency and embryonic development [3][15]. Group 1: Research Findings - The study published by Professor Wu Jun's team at the University of Texas Southwestern Medical Center demonstrates that enforced mitophagy can lead to a reduction in mitochondrial quantity, which subsequently delays pre-implantation embryonic development in mice [3][11]. - The research indicates that pluripotent stem cells (PSCs) lacking mitochondria can survive for 3-5 days in vitro but cease to divide, suggesting that these cells can compensate for the absence of mitochondria by taking over energy production and other functions typically performed by mitochondria [8][13]. - The study also reveals that the enforced mitophagy method can be applied across different species and cell types, potentially opening new avenues for research and treatment of mitochondrial diseases [8][15]. Group 2: Methodology - The enforced mitophagy technique involves expressing the PRKN protein in cells, which promotes the degradation of dysfunctional mitochondria, followed by treatment with mitochondrial uncouplers to stimulate extensive mitophagy [6][8]. - The research team successfully generated PSCs devoid of mitochondria and assessed the gene expression changes, finding that 788 genes became less active while 1696 genes became more active, indicating a shift in cellular function [8][13]. - The study further explores the fusion of human PSCs with those from non-human primates, revealing that these hybrid cells selectively retain human mitochondrial DNA, demonstrating the interchangeability of mitochondrial support for pluripotency across species [9][13]. Group 3: Implications - The findings suggest that a significant reduction in mitochondrial content can hinder embryonic development, with a 65% loss leading to implantation failure and a 33% loss resulting in developmental delays [11][13]. - The research provides a powerful tool for investigating the roles of mitochondria in cellular functions, organ development, aging, and evolutionary biology, potentially impacting future therapeutic strategies for mitochondrial diseases [15].