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从衰老体细胞高效构建猴囊胚样结构

Highly efficient construction of monkey blastoid capsules from aged somatic cells.

作者信息

Wu Junmo, Shao Tianao, Tang Zengli, Liu Gaojing, Li Zhuoyao, Shi Yuxi, Kang Yu, Zuo Jiawei, Zhao Bo, Hu Guangyu, Liu Jiaqi, Ji Weizhi, Zhang Lei, Niu Yuyu

机构信息

State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.

Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, China.

出版信息

Nat Commun. 2025 Jan 28;16(1):1130. doi: 10.1038/s41467-025-56447-z.

DOI:10.1038/s41467-025-56447-z
PMID:39875393
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11775175/
Abstract

Blastoids-blastocyst-like structures created in vitro-emerge as a valuable model for early embryonic development research. Non-human primates stem cell-derived blastoids are an ethically viable alternative to human counterparts, yet the low formation efficiency of monkey blastoid cavities, typically below 30%, has limited their utility. Prior research has predominantly utilized embryonic stem cells. In this work, we demonstrate the efficient generation of blastoids from induced pluripotent stem cells and somatic cell nuclear transfer embryonic stem cells derived from aged monkeys, achieving an 80% formation efficiency. We also introduce a hydrogel-based microfluidics platform for the scalable and reproducible production of size-adjustable, biodegradable blastoid capsules, providing a stable 3D structure and mechanical protection. This advancement in the high-efficiency, scalable production of monkey blastoid capsules from reprogrammed aged somatic cells significantly enhances the study of embryonic development and holds promise for regenerative medicine.

摘要

胚状体——体外创建的类囊胚结构——成为早期胚胎发育研究的宝贵模型。非人灵长类动物干细胞衍生的胚状体在伦理上是人类胚状体的可行替代方案,但猴子胚状体腔的形成效率较低,通常低于30%,这限制了它们的实用性。先前的研究主要使用胚胎干细胞。在这项工作中,我们展示了从老年猴子诱导多能干细胞和体细胞核移植胚胎干细胞高效生成胚状体,形成效率达到80%。我们还引入了一种基于水凝胶的微流控平台,用于可扩展且可重复地生产尺寸可调、可生物降解的胚状体胶囊,并提供稳定的三维结构和机械保护。从重新编程的老年体细胞高效、可扩展地生产猴子胚状体胶囊的这一进展显著增强了胚胎发育研究,并为再生医学带来了希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/eb6348f2e8fb/41467_2025_56447_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/22b7466eba91/41467_2025_56447_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/9d2034daa6b7/41467_2025_56447_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/82a245a3854d/41467_2025_56447_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/23c2577fdc44/41467_2025_56447_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/90c4722b0c53/41467_2025_56447_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/01a1b5ebe590/41467_2025_56447_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/9c7f0d250b30/41467_2025_56447_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/eb6348f2e8fb/41467_2025_56447_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/22b7466eba91/41467_2025_56447_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/9d2034daa6b7/41467_2025_56447_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/82a245a3854d/41467_2025_56447_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/23c2577fdc44/41467_2025_56447_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/90c4722b0c53/41467_2025_56447_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/01a1b5ebe590/41467_2025_56447_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/9c7f0d250b30/41467_2025_56447_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36dd/11775175/eb6348f2e8fb/41467_2025_56447_Fig8_HTML.jpg

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本文引用的文献

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Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously.自更新的人类原始多能干细胞在 3D 培养中去分化,并自发形成胚状体。
Nat Commun. 2024 Jan 22;15(1):668. doi: 10.1038/s41467-024-44969-x.
2
Current state of stem cell research in non-human primates: an overview.非人灵长类动物干细胞研究的现状:综述
Med Rev (2021). 2023 Nov 6;3(4):277-304. doi: 10.1515/mr-2023-0035. eCollection 2023 Aug.
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Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.
胚胎与胚外谱系细胞的相互作用与干细胞共培养。
Cell. 2023 Dec 21;186(26):5859-5875.e24. doi: 10.1016/j.cell.2023.11.008. Epub 2023 Dec 4.
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Long-term in vivo chimeric cells tracking in non-human primate.在非人灵长类动物中长期体内嵌合细胞的示踪。
Protein Cell. 2024 Feb 29;15(3):207-222. doi: 10.1093/procel/pwad049.
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Large-scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal cross talk.大规模生产人类类囊胚,可用于模拟囊胚发育和母体-胎儿对话。
Cell Stem Cell. 2023 Sep 7;30(9):1246-1261.e9. doi: 10.1016/j.stem.2023.08.002.
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3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages.三维培养海胆模型再现人类从着床前到早期原肠胚发生阶段的胚胎发生过程。
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