Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.
Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.
复制标题
绘制人体内子宫内膜和体外子宫内膜的时间和空间动力学。
DOI：
10.1038/s41588-021-00972-2
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发表时间：
2021-12
期刊：
影响因子：
30.8
通讯作者：
Vento-Tormo R
中科院分区：
文献类型：
--
作者：
Garcia-Alonso L;Handfield LF;Roberts K;Nikolakopoulou K;Fernando RC;Gardner L;Woodhams B;Arutyunyan A;Polanski K;Hoo R;Sancho-Serra C;Li T;Kwakwa K;Tuck E;Lorenzi V;Massalha H;Prete M;Kleshchevnikov V;Tarkowska A;Porter T;Mazzeo CI;van Dongen S;Dabrowska M;Vaskivskyi V;Mahbubani KT;Park JE;Jimenez-Linan M;Campos L;Kiselev VY;Lindskog C;Ayuk P;Prigmore E;Stratton MR;Saeb-Parsy K;Moffett A;Moore L;Bayraktar OA;Teichmann SA;Turco MY;Vento-Tormo R
子宫内膜，子宫的粘膜衬里，在整个月经周期中对卵巢激素的反应发生动态变化。我们已经生成了密集的单细胞和空间参考地图的人类子宫和三维子宫内膜类器官培养。我们剖析了在管腔和腺体微环境中决定上皮谱系细胞命运的信号通路。我们的子宫内膜类器官的基准揭示了体内和体外调节分泌和纤毛谱系分化的途径和细胞状态。体外下调WNT或NOTCH通路分别提高分泌系和纤毛系分化效率。我们利用我们的细胞图谱对来自子宫内膜癌和子宫内膜异位症病变的大量数据进行解卷，阐明在这些疾病中占主导地位的细胞类型。这些机制的见解为未来治疗包括子宫内膜异位症和子宫内膜癌在内的常见疾病提供了一个平台。人类子宫内膜的单细胞和空间转录组学分析强调了控制月经周期增殖和分泌阶段的途径。对子宫内膜类器官的分析表明，WNT和NOTCH信号分别调节向分泌上皮和纤毛上皮分化。
The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma. Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively.
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DOI：
10.1097/igc.0000000000001061
发表时间：
2017-10
期刊：
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
影响因子：
--
作者：
Girda E;Huang EC;Leiserowitz GS;Smith LH
通讯作者：
Smith LH
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.9
作者：
Andersson A;Bergenstråhle J;Asp M;Bergenstråhle L;Jurek A;Fernández Navarro J;Lundeberg J
通讯作者：
Lundeberg J
影响因子：
4.6
作者：
Boretto, Matteo;Cox, Benoit;Vankelecom, Hugo
通讯作者：
Vankelecom, Hugo
影响因子：
8.8
作者：
Barker, Nick;Rookmaaker, Maarten B.;Clevers, Hans
通讯作者：
Clevers, Hans