单细胞转录组学鉴定了 WNT7A-FZD5 信号轴，该信号轴在患者来源的类器官中维持输卵管干细胞。
Single-cell transcriptomics identifies a WNT7A-FZD5 signaling axis that maintains fallopian tube stem cells in patient-derived organoids.
发表日期：2023 Oct 31
作者：
Abdulkhaliq Alsaadi, Mara Artibani, Zhiyuan Hu, Nina Wietek, Matteo Morotti, Laura Santana Gonzalez, Moiad Alazzam, Jason Jiang, Beena Abdul, Hooman Soleymani Majd, Levi L Blazer, Jarret Adams, Francesca Silvestri, Sachdev S Sidhu, Joan S Brugge, Ahmed Ashour Ahmed
来源：
Stem Cell Research & Therapy
摘要：
由于对 FT 干细胞的了解有限以及缺乏干细胞更新和分化的体外模型，输卵管 (FT) 在健康和疾病中的功能研究受到阻碍。使用优化的类器官培养条件来解决这些限制，我们发现 FT 干细胞更新高度依赖于 WNT/β-连环蛋白信号传导，并设计内源性 WNT/β-连环蛋白信号传导报告类器官来对这些细胞进行生物标记、分离和表征。使用功能方法以及批量和单细胞转录组学分析，我们表明内源激素调节的 WNT7A-FZD5 信号轴对于干细胞更新至关重要，并且 WNT/β-连环蛋白途径激活的细胞形成了独特的转录组簇FT 细胞富含细胞外基质 (ECM) 重塑和整合素信号通路。总的来说，我们对 FT 干细胞及其自我更新的分子要求进行了深入的描述，为研究干细胞在 FT 健康和疾病中的作用的机制工作铺平了道路。版权所有 © 2023。由 Elsevier Inc. 出版。
The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge of FT stem cells and lack of in vitro models of stem cell renewal and differentiation. Using optimized organoid culture conditions to address these limitations, we find that FT stem cell renewal is highly dependent on WNT/β-catenin signaling and engineer endogenous WNT/β-catenin signaling reporter organoids to biomark, isolate, and characterize these cells. Using functional approaches, as well as bulk and single-cell transcriptomics analyses, we show that an endogenous hormonally regulated WNT7A-FZD5 signaling axis is critical for stem cell renewal and that WNT/β-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in extracellular matrix (ECM) remodeling and integrin signaling pathways. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease.Copyright © 2023. Published by Elsevier Inc.