Estrogen receptor alpha regulates uterine epithelial lineage specification and homeostasis.
Estrogen receptor alpha regulates uterine epithelial lineage specification and homeostasis.
复制标题
DOI：
10.1016/j.isci.2023.107568
复制
发表时间：
2023-09-15
期刊：
影响因子：
5.8
通讯作者：
Kelleher, Andrew M.
中科院分区：
文献类型：
--
作者：
Rizo, Jason A.;Davenport, Kimberly M.;Winuthayanon, Wipawee;Spencer, Thomas E.;Kelleher, Andrew M.
出生后子宫的发育包括未分化上皮向子宫型上皮的分化。这种特异性受基质-上皮相互作用以及内在细胞特异性转录因子和基因调控网络的调节。本研究利用Esr 1缺失、子宫内膜上皮类器官（EEO）和类器官-基质共培养的小鼠遗传模型来解读Esr 1在子宫上皮发育中的作用。来自野生型（WT）小鼠的类器官发育为正常的单层柱状上皮。与此相反，EEO从Esr 1基因敲除小鼠发展成多层复层鳞状上皮与基底细胞。将Esr 1缺失上皮与WT子宫基质成纤维细胞共培养抑制基底细胞发育。值得注意的是，EEO-基质共培养物和Esr 1条件性敲除小鼠的雌激素治疗增加了基底上皮细胞标志物。总的来说，这些研究结果表明，ESR 1调节子宫上皮谱系可塑性和稳态和ESR 1的损失促进改变腔基底分化驱动的ESR 1介导的旁分泌因子从基质。ESR 1是子宫上皮类器官发育所必需的缺乏上皮ESR 1驱动腔-基底分化子宫内膜基质细胞控制ESR 1阴性上皮可塑性基质介导的E2信号影响ESR 1阴性上皮分化分子生物学;细胞生物学;发育生物学;组学;转录组学
Postnatal development of the uterus involves specification of undifferentiated epithelium into uterine-type epithelium. That specification is regulated by stromal-epithelial interactions as well as intrinsic cell-specific transcription factors and gene regulatory networks. This study utilized mouse genetic models of Esr1 deletion, endometrial epithelial organoids (EEO), and organoid-stromal co-cultures to decipher the role of Esr1 in uterine epithelial development. Organoids derived from wild-type (WT) mice developed a normal single layer of columnar epithelium. In contrast, EEO from Esr1 null mice developed a multilayered stratified squamous type of epithelium with basal cells. Co-culturing Esr1 null epithelium with WT uterine stromal fibroblasts inhibited basal cell development. Of note, estrogen treatment of EEO-stromal co-cultures and Esr1 conditional knockout mice increased basal epithelial cell markers. Collectively, these findings suggest that Esr1 regulates uterine epithelium lineage plasticity and homeostasis and loss of ESR1 promotes altered luminal-to-basal differentiation driven by ESR1-mediated paracrine factors from the stroma. ESR1 is required for uterine epithelial organoid development Absence of epithelial ESR1 drives luminal-to-basal differentiation Endometrial stromal cells govern ESR1-negative epithelial plasticity Stroma-mediated E2 signaling impacts ESR1-negative epithelial differentiation Molecular biology; Cell biology; Developmental biology; Omics; Transcriptomics
登录
查看更多内容
影响因子：
4.6
作者：
Holthaus KB;Lachner J;Ebner B;Tschachler E;Eckhart L
通讯作者：
Eckhart L
DOI：
10.1002/path.5069
发表时间：
2018-06
期刊：
The Journal of pathology
影响因子：
--
作者：
Son J;Park Y;Chung SH
通讯作者：
Chung SH
影响因子：
4.6
作者：
Boretto, Matteo;Cox, Benoit;Vankelecom, Hugo
通讯作者：
Vankelecom, Hugo
影响因子：
2.9
作者：
HOHL, D;OLANO, BR;ROOP, DR
通讯作者：
ROOP, DR
影响因子：
3.8
作者：
Kabos, Peter;Haughian, James M.;Wang, Xinshuo;Dye, Wendy W.;Finlayson, Christina;Elias, Anthony;Horwitz, Kathryn B.;Sartorius, Carol A.
通讯作者：
Sartorius, Carol A.