建立模拟乳腺发育和泌乳的山羊乳腺类器官培养物。

IF 6.3 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Journal of Animal Science and Biotechnology Pub Date : 2024-10-01 DOI:10.1186/s40104-024-01084-7
Lei Jia, Wenying Zhang, Tao Luo, Yongtao Li, Jianhong Shu, Julie Strand, Yuan Yue, Stig Purup, Jianxin Liu, Hengbo Shi
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引用次数: 0

摘要

背景:虽然已开发出几种细胞培养系统来研究奶畜乳腺的功能,但它们都有潜在的局限性,如失去乳腺泡结构或与本地对应物存在遗传和表型差异。克服这些挑战对泌乳研究至关重要。开发建立家畜泌乳类器官的方案是未来一个很有希望的目标。在这项研究中,我们制定了一套方案来建立奶山羊乳腺器官组织的培养系统,以模拟乳腺发育和泌乳过程:结果:在细胞外基质凝胶中培养的有机体保持了与乳腺组织原生结构非常相似的双层结构。含有表皮生长因子和成纤维细胞生长因子2的生长因子能显著促进乳腺器官组织的扩张,而WNT抑制剂则能显著抑制器官组织的增殖指数。在含有催乳素的泌乳培养基的刺激下,乳腺器官组织表现出高效的泌乳,其特征是腔隙中脂滴的积累。泌乳可持续3周以上。重要的是,泌乳器官组织中与脂肪酸合成和乳蛋白相关基因的表达模式与乳腺组织中观察到的模式非常相似。这些观察结果得到了蛋白质组分析数据的证实,即大部分乳蛋白是在泌乳器官组织中产生的:本研究首次建立了反刍动物乳腺发育和泌乳过程的乳腺类器官培养系统模型。该研究首次建立了反刍动物乳腺发育和泌乳过程的乳腺类器官培养系统模型。在反刍动物乳腺类器官中高效诱导泌乳,有望推动食品工业中基于细胞的牛奶生物制造领域的发展。
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Establishment of goat mammary organoid cultures modeling the mammary gland development and lactation.

Background: Although several cell culture systems have been developed to investigate the function of the mammary gland in dairy livestock, they have potential limitations, such as the loss of alveolar structure or genetic and phenotypic differences from their native counterparts. Overcoming these challenges is crucial for lactation research. Development of protocols to establish lactating organoid of livestock represents a promising goal for the future. In this study, we developed a protocol to establish a culture system for mammary organoids in dairy goats to model the mammary gland development and lactation process.

Results: The organoids cultured within an extracellular matrix gel maintained a bilayer structure that closely resembled the native architecture of mammary tissue. The expansion of mammary organoids was significantly promoted by growth factors containing epidermal growth factor and fibroblast growth factor 2 whereas the proliferative index of the organoids was significantly inhibited by the treatment with WNT inhibitors. Upon stimulation with a lactogenic medium containing prolactin, the mammary organoids exhibited efficient lactation, characterized by the accumulation of lipid droplets in the lumen space. The lactation could be sustained for more than 3 weeks. Importantly, the expression patterns of genes related to fatty acid synthesis and milk proteins in lactating organoids closely mirrored those observed in mammary tissues. These observations were confirmed by data from proteomic analysis that the bulk of milk proteins was produced in the lactating organoids.

Conclusion: This study is the first to establish a mammary organoid culture system modeling the mammary gland development and lactation process in ruminants. The efficient induction of lactation in ruminant mammary organoids holds promises for advancing the field of cell-based milk bio-manufacture in the food industry.

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CiteScore
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822
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