Progesterone Signaling in Endometrial Epithelial Organoids.
Progesterone Signaling in Endometrial Epithelial Organoids.
复制标题
子宫内膜上皮器官中的孕酮信号传导。
作者：
为了建立妊娠，子宫细胞通过其核受体、雌激素受体 (ESR1) 和孕激素受体 (PGR) 对卵巢激素、雌激素和孕激素做出反应。 ESR1 和 PGR 通过在基因和远端增强子区域结合染色质来调节基因，这两个区域通过动态 3 维染色质结构相互作用。子宫内膜上皮细胞是胚胎附着和侵袭的初始部位，因此了解产生其接受状态的过程非常重要。在这里，我们培养并处理从子宫内膜活检中分离出的人类上皮细胞衍生的类器官，并用雌激素和黄体酮进行处理，并评估了它们的转录谱、PGR 顺反组和染色质构象。黄体酮减弱了雌激素依赖性基因反应，但对类器官转录组的影响微乎其微。 PGR ChIPseq 峰与之前描述的类器官 ESR1 峰共定位，并且大多数 PGR 和 ESR1 峰位于染色质的 B（非活性）区室区域。通过考虑使用 HiC 识别的染色质环，与使用相对于最接近基因的 ESR1 峰位置识别的染色质环相比，明显更多的 ESR1 峰被分配给雌激素调节基因。总体而言，类器官模型可以定义控制激素反应性的染色质调节成分。
For pregnancy to be established, uterine cells respond to the ovarian hormones, estrogen, and progesterone, via their nuclear receptors, the estrogen receptor (ESR1) and progesterone receptor (PGR). ESR1 and PGR regulate genes by binding chromatin at genes and at distal enhancer regions, which interact via dynamic 3-dimensional chromatin structures. Endometrial epithelial cells are the initial site of embryo attachment and invasion, and thus understanding the processes that yield their receptive state is important. Here, we cultured and treated organoids derived from human epithelial cells, isolated from endometrial biopsies, with estrogen and progesterone and evaluated their transcriptional profiles, their PGR cistrome, and their chromatin conformation. Progesterone attenuated estrogen-dependent gene responses but otherwise minimally impacted the organoid transcriptome. PGR ChIPseq peaks were co-localized with previously described organoid ESR1 peaks, and most PGR and ESR1 peaks were in B (inactive) compartment regions of chromatin. Significantly more ESR1 peaks were assigned to estrogen-regulated genes by considering chromatin loops identified using HiC than were identified using ESR1 peak location relative to closest genes. Overall, the organoids model allowed a definition of the chromatin regulatory components governing hormone responsiveness.
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影响因子：
5.5
作者：
Heremans R;Jan Z;Timmerman D;Vankelecom H
通讯作者：
Vankelecom H
DOI：
10.1196/annals.1429.018
发表时间：
2008-01-01
期刊：
MENSTRUAL CYCLE AND ADOLESCENT HEALTH
影响因子：
--
作者：
Hawkinsa, Shannon M.;Matzuk, Martin M.
通讯作者：
Matzuk, Martin M.
影响因子：
4.8
作者：
Franco, Heather L.;Rubel, Cory A.;DeMayo, Francesco J.
通讯作者：
DeMayo, Francesco J.
影响因子：
--
作者：
Hewitt, SC;Deroo, BJ;Korach, KS
通讯作者：
Korach, KS
影响因子：
16.8
作者：
Lerdrup, Mads;Johansen, Jens Vilstrup;Hansen, Klaus
通讯作者：
Hansen, Klaus