Stowers Institute for Medical Research, Kansas City, United States.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, United States.
Elife. 2024 Jun 14;13:RP92844. doi: 10.7554/eLife.92844.
Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it's unclear whether they exist during developmental EMT. Neural crest cells (NCC) are an embryonic progenitor cell population that gives rise to numerous cell types and tissues in vertebrates, and their formation and delamination is a classic example of developmental EMT. However, whether intermediate states also exist during NCC EMT and delamination remains unknown. Through single-cell RNA sequencing of mouse embryos, we identified intermediate NCC states based on their transcriptional signature and then spatially defined their locations in situ in the dorsolateral neuroepithelium. Our results illustrate the importance of cell cycle regulation and functional role for the intermediate stage marker in facilitating mammalian cranial NCC delamination and may provide new insights into mechanisms regulating pathological EMP.
上皮-间充质转化(EMT)是一种细胞过程,可将上皮细胞转化为具有迁移潜能的间充质细胞,这一过程存在于发育和病理过程中。尽管 EMT 最初被认为是一个二元事件,但在癌症进展过程中,EMT 涉及到完全上皮和完全间充质表型之间的中间状态,这些状态的特征是上皮和间充质标志物的不同组合。这种现象被称为上皮-间充质可塑性(EMP),然而,中间状态仍然描述不足,并且不清楚它们是否存在于发育 EMT 过程中。神经嵴细胞(NCC)是一种胚胎祖细胞群体,可在脊椎动物中产生多种细胞类型和组织,其形成和分离是发育 EMT 的经典范例。然而,NCC EMT 和分离过程中是否也存在中间状态尚不清楚。通过对小鼠胚胎进行单细胞 RNA 测序,我们根据其转录特征确定了中间 NCC 状态,然后在原位空间定义了它们在背外侧神经上皮中的位置。我们的研究结果说明了细胞周期调控的重要性和中间阶段标志物在促进哺乳动物颅神经嵴细胞分离中的功能作用,这可能为调节病理性 EMP 的机制提供新的见解。
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