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Capture and metabolomic analysis of the human endometrial epithelial organoid secretome [Cell Biology]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2021-04-13 , DOI: 10.1073/pnas.2026804118
Constantine A. Simintiras, Pramod Dhakal, Chaman Ranjit, Harriet C. Fitzgerald, Ahmed Z. Balboula, Thomas E. Spencer

Suboptimal uterine fluid (UF) composition can lead to pregnancy loss and likely contributes to offspring susceptibility to chronic adult-onset disorders. However, our understanding of the biochemical composition and mechanisms underpinning UF formation and regulation remain elusive, particularly in humans. To address this challenge, we developed a high-throughput method for intraorganoid fluid (IOF) isolation from human endometrial epithelial organoids. The IOF is biochemically distinct to the extraorganoid fluid (EOF) and cell culture medium as evidenced by the exclusive presence of 17 metabolites in IOF. Similarly, 69 metabolites were unique to EOF, showing asymmetrical apical and basolateral secretion by the in vitro endometrial epithelium, in a manner resembling that observed in vivo. Contrasting the quantitative metabolomic profiles of IOF and EOF revealed donor-specific biochemical signatures of organoids. Subsequent RNA sequencing of these organoids from which IOF and EOF were derived established the capacity to readily perform organoid multiomics in tandem, and suggests that transcriptomic regulation underpins the observed secretory asymmetry. In summary, these data provided by modeling uterine luminal and basolateral fluid formation in vitro offer scope to better understand UF composition and regulation with potential impacts on female fertility and offspring well-being.



中文翻译:

人子宫内膜上皮类器官分泌物组的捕获和代谢组学分析[细胞生物学]

子宫液(UF)欠佳会导致流产,并可能导致后代易患慢性成年性疾病。但是,我们对UF形成和调控的生化成分和机制的了解仍然难以捉摸,尤其是在人类中。为了解决这一挑战,我们开发了一种高通量方法,用于从人子宫内膜上皮类器官中分离有机体内流体(IOF)。IOF在生物化学上不同于有机外流体(EOF)和细胞培养基,这是由IOF中仅存在17种代谢物所证明的。同样,69种代谢物是EOF特有的,在体外子宫内膜上皮细胞中表现出不对称的顶端和基底外侧分泌,其方式类似于在体内观察到的方式。对比IOF和EOF的定量代谢组学谱,揭示了类器官的供体特异性生化特征。随后从中衍生出IOF和EOF的这些类器官的RNA测序建立了易于串联执行类器官多体组学的能力,并表明转录组调控是所观察到的分泌不对称的基础。总而言之,这些通过体外模拟子宫腔和基底外侧液形成而提供的数据为更好地了解超滤成分和对女性生育力和后代福祉的潜在影响的调节提供了范围。并提示转录组调控是观察到的分泌不对称的基础。总而言之,这些通过体外模拟子宫腔和基底外侧液形成而提供的数据为更好地了解超滤成分和对女性生育力和后代福祉的潜在影响的调节提供了范围。并提示转录组调控是观察到的分泌不对称的基础。总而言之,这些通过体外模拟子宫腔和基底外侧液形成而提供的数据为更好地了解超滤成分和对女性生育力和后代福祉的潜在影响的调节提供了范围。

更新日期:2021-04-06
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