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体细胞核移植克隆:整合技术和生物学驱动的进展。

Cloning by SCNT: Integrating Technical and Biology-Driven Advances.

机构信息

Chemical Biology Graduate Program, Federal University of São Paulo - UNIFESP, Campus Diadema, Diadema - SP, Brazil.

出版信息

Methods Mol Biol. 2023;2647:1-35. doi: 10.1007/978-1-0716-3064-8_1.

DOI:10.1007/978-1-0716-3064-8_1
PMID:37041327
Abstract

Somatic cell nuclear transfer (SCNT) into enucleated oocytes initiates nuclear reprogramming of lineage-committed cells to totipotency. Pioneer SCNT work culminated with cloned amphibians from tadpoles, while technical and biology-driven advances led to cloned mammals from adult animals. Cloning technology has been addressing fundamental questions in biology, propagating desired genomes, and contributing to the generation of transgenic animals or patient-specific stem cells. Nonetheless, SCNT remains technically complex and cloning efficiency relatively low. Genome-wide technologies revealed barriers to nuclear reprogramming, such as persistent epigenetic marks of somatic origin and reprogramming resistant regions of the genome. To decipher the rare reprogramming events that are compatible with full-term cloned development, it will likely require technical advances for large-scale production of SCNT embryos alongside extensive profiling by single-cell multi-omics. Altogether, cloning by SCNT remains a versatile technology, while further advances should continuously refresh the excitement of its applications.

摘要

体细胞核移植(SCNT)将核供体细胞注入去核卵母细胞中,启动了谱系限定细胞向全能性的核重编程。先驱性的 SCNT 工作以克隆蛙类幼体为高潮,而技术和生物学驱动的进步则导致了成年动物的克隆哺乳动物。克隆技术一直在解决生物学中的基本问题,复制所需的基因组,并有助于生成转基因动物或患者特异性干细胞。尽管如此,SCNT 仍然具有技术复杂性,克隆效率相对较低。全基因组技术揭示了核重编程的障碍,例如体细胞来源的持续表观遗传标记和基因组中重编程抗性区域。为了解释与完全克隆发育相容的罕见重编程事件,可能需要在大规模生产 SCNT 胚胎的同时,通过单细胞多组学进行广泛的分析,来实现技术上的进步。总之,SCNT 仍然是一种多功能技术,而进一步的进展应该不断刷新其应用的兴奋点。

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本文引用的文献

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Epigenetics, DNA damage, and aging.表观遗传学、DNA 损伤与衰老。
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β cell regeneration and novel strategies for treatment of diabetes (Review).β细胞再生与糖尿病治疗新策略(综述)
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