Rizo Jason A, Davenport Kimberly M, Winuthayanon Wipawee, Spencer Thomas E, Kelleher Andrew M
Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
Department of Obstetrics, Gynecology, and Women's Health, University of Missouri, Columbia, MO 65211, USA.
iScience. 2023 Aug 9;26(9):107568. doi: 10.1016/j.isci.2023.107568. eCollection 2023 Sep 15.
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 deletion, endometrial epithelial organoids (EEO), and organoid-stromal co-cultures to decipher the role of in uterine epithelial development. Organoids derived from wild-type (WT) mice developed a normal single layer of columnar epithelium. In contrast, EEO from null mice developed a multilayered stratified squamous type of epithelium with basal cells. Co-culturing null epithelium with WT uterine stromal fibroblasts inhibited basal cell development. Of note, estrogen treatment of EEO-stromal co-cultures and conditional knockout mice increased basal epithelial cell markers. Collectively, these findings suggest that 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.
子宫的产后发育涉及未分化上皮向子宫型上皮的特化。这种特化受基质 - 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。本研究利用基因缺失的小鼠遗传模型、子宫内膜上皮类器官（EEO）和类器官 - 基质共培养来解读其在子宫上皮发育中的作用。源自野生型（WT）小鼠的类器官形成了正常的单层柱状上皮。相比之下，来自基因敲除小鼠的EEO形成了具有基底细胞的多层复层鳞状上皮。将基因敲除的上皮与WT子宫基质成纤维细胞共培养可抑制基底细胞的发育。值得注意的是，对EEO - 基质共培养物和条件性基因敲除小鼠进行雌激素处理可增加基底上皮细胞标志物。总体而言，这些发现表明其调节子宫上皮谱系可塑性和稳态，而ESR1的缺失会促进由ESR1介导的来自基质的旁分泌因子驱动的腔面到基底分化的改变。
