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通过化学重编程获得的无转基因小鼠胚胎模型进入早期器官发生阶段。

Transgene-free mouse embryo models from chemical reprogramming reach early organogenesis.

作者信息

Yu Xiu, Wang Jichang

机构信息

Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangzhou, 510080, China.

Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.

出版信息

Cell Regen. 2025 Sep 4;14(1):37. doi: 10.1186/s13619-025-00259-5.

DOI:10.1186/s13619-025-00259-5
PMID:40906301
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12411326/
Abstract

Embryo models derived from pluripotent stem cells (PSCs) have become powerful tools for dissecting mammalian embryonic development and advancing regenerative medicine. Two recent studies in Cell and Cell Stem Cell report major advances in generating mouse embryo models that replicate development up to early organogenesis (equivalent to embryonic day 8.5~8.75). Li et al. describe a purely chemical strategy to reprogram mouse embryonic stem cells (mESCs) into induced embryo founder cells (iEFCs) capable of forming complete embryo models (iEFC-EMs). In parallel, Yilmaz et al. demonstrate transgene-free generation of post-gastrulation models (TF-SEMs) from naive mESCs and induced pluripotent stem cells (iPSCs) using a similar chemical cocktail. Both models faithfully recapitulate key developmental events, including gastrulation, neural tube formation, cardiogenesis, and somitogenesis. These advances not only deepen understanding of early mammalian development but also pave the way for applications in regenerative medicine and disease modeling.

摘要

源自多能干细胞(PSC)的胚胎模型已成为剖析哺乳动物胚胎发育和推进再生医学的强大工具。《细胞》和《细胞干细胞》杂志最近的两项研究报告了在生成小鼠胚胎模型方面取得的重大进展,这些模型可复制直至早期器官发生阶段(相当于胚胎第8.5至8.75天)的发育过程。李等人描述了一种纯粹的化学策略,可将小鼠胚胎干细胞(mESC)重编程为能够形成完整胚胎模型(iEFC-EM)的诱导胚胎起始细胞(iEFC)。与此同时,伊尔马兹等人展示了使用类似的化学混合物从原始mESC和诱导多能干细胞(iPSC)无转基因生成原肠胚形成后模型(TF-SEM)。这两种模型都忠实地再现了关键的发育事件,包括原肠胚形成、神经管形成、心脏发生和体节发生。这些进展不仅加深了对早期哺乳动物发育的理解,也为再生医学和疾病建模的应用铺平了道路。

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本文引用的文献

1
A complete model of mouse embryogenesis through organogenesis enabled by chemically induced embryo founder cells.通过化学诱导的胚胎起始细胞实现的直至器官发生阶段的小鼠胚胎发育完整模型。
Cell. 2025 Aug 7. doi: 10.1016/j.cell.2025.07.018.
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Transgene-free generation of mouse post-gastrulation whole embryo models solely from naive ESCs and iPSCs.仅从原始胚胎干细胞和诱导多能干细胞无转基因生成小鼠原肠胚形成后的全胚胎模型。
Cell Stem Cell. 2025 Aug 7. doi: 10.1016/j.stem.2025.07.005.
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The primitive endoderm supports lineage plasticity to enable regulative development.原始内胚层支持谱系可塑性以实现调节发育。
Cell. 2024 Jul 25;187(15):4010-4029.e16. doi: 10.1016/j.cell.2024.05.051. Epub 2024 Jun 24.
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Hypoblast from human pluripotent stem cells regulates epiblast development.人类多能干细胞的下胚层调节上胚层发育。
Nature. 2024 Feb;626(7998):357-366. doi: 10.1038/s41586-023-06871-2. Epub 2023 Dec 5.
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Embryo model completes gastrulation to neurulation and organogenesis.胚胎模型完成原肠胚形成至神经胚形成和器官发生。
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Establishment of mouse stem cells that can recapitulate the developmental potential of primitive endoderm.建立能够重现原始内胚层发育潜力的小鼠干细胞。
Science. 2022 Feb 4;375(6580):574-578. doi: 10.1126/science.aay3325. Epub 2022 Feb 3.
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Construction of a mammalian embryo model from stem cells organized by a morphogen signalling centre.由形态发生信号中心组织的干细胞构建哺乳动物胚胎模型。
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Retinoic acid signaling is critical during the totipotency window in early mammalian development.视黄酸信号在早期哺乳动物发育的全能性窗口期间至关重要。
Nat Struct Mol Biol. 2021 Jun;28(6):521-532. doi: 10.1038/s41594-021-00590-w. Epub 2021 May 27.