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建立和表征龟类肝脏类器官为解码其独特适应性提供了一个潜在的模型。

Establishment and characterization of turtle liver organoids provides a potential model to decode their unique adaptations.

机构信息

SMART Pharmacology, Department of Biomedical Sciences, Iowa State University, Ames, IA, USA.

3D Health Solutions Inc., Ames, IA, USA.

出版信息

Commun Biol. 2024 Feb 22;7(1):218. doi: 10.1038/s42003-024-05818-1.

DOI:10.1038/s42003-024-05818-1
PMID:38388772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10883927/
Abstract

Painted turtles are remarkable for their freeze tolerance and supercooling ability along with their associated resilience to hypoxia/anoxia and oxidative stress, rendering them an ideal biomedical model for hypoxia-induced injuries (including strokes), tissue cooling during surgeries, and organ cryopreservation. Yet, such research is hindered by their seasonal reproduction and slow maturation. Here we developed and characterized adult stem cell-derived turtle liver organoids (3D self-assembled in vitro structures) from painted, snapping, and spiny softshell turtles spanning ~175My of evolution, with a subset cryopreserved. This development is, to the best of our knowledge, a first for this vertebrate Order, and complements the only other non-avian reptile organoids from snake venom glands. Preliminary characterization, including morphological, transcriptomic, and proteomic analyses, revealed organoids enriched in cholangiocytes. Deriving organoids from distant turtles and life stages demonstrates that our techniques are broadly applicable to chelonians, permitting the development of functional genomic tools currently lacking in herpetological research. Such platform could potentially support studies including genome-to-phenome mapping, gene function, genome architecture, and adaptive responses to climate change, with implications for ecological, evolutionary, and biomedical research.

摘要

彩龟以其抗冻能力和过冷能力以及对缺氧/缺氧和氧化应激的相关恢复能力而闻名,这使它们成为研究缺氧引起的损伤(包括中风)、手术中组织冷却和器官冷冻保存的理想生物医学模型。然而,这种研究受到其季节性繁殖和缓慢成熟的阻碍。在这里,我们从跨越约 1.75 亿年进化史的彩龟、 snapping 龟和刺鳖开发并表征了成年干细胞衍生的龟肝类器官(3D 体外自组装结构),其中一部分被冷冻保存。据我们所知,这是该脊椎动物目首次开发出这种类器官,与其他仅来自蛇毒腺的非鸟类爬行动物类器官互补。初步表征,包括形态、转录组和蛋白质组分析,揭示了类器官富含胆管细胞。从不同的龟和生命阶段获得类器官表明,我们的技术广泛适用于龟鳖类,为缺乏爬行动物研究的功能基因组工具的开发提供了可能。该平台可能支持包括从基因组到表型图谱、基因功能、基因组结构和对气候变化的适应性反应在内的研究,对生态、进化和生物医学研究具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/157b5c21718f/42003_2024_5818_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/5e535eaa0d29/42003_2024_5818_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/c07ed8fe0d0e/42003_2024_5818_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/9dacd9ebd0a5/42003_2024_5818_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/0a270f814d05/42003_2024_5818_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/157b5c21718f/42003_2024_5818_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/5e535eaa0d29/42003_2024_5818_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/c07ed8fe0d0e/42003_2024_5818_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/9dacd9ebd0a5/42003_2024_5818_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/0a270f814d05/42003_2024_5818_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e432/10883927/157b5c21718f/42003_2024_5818_Fig5_HTML.jpg

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