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Alsaadi, Abdulkhaliq; Artibani, Mara; Hu, Zhiyuan; Wietek, Nina; Morotti, Matteo; Gonzalez, Laura Santana; Alazzam, Moiad; Jiang, Jason; Abdul, Beena; Soleymani majd, Hooman; Blazer, Levi L.; Adams, Jarret; Silvestri, Francesca; Sidhu, Sachdev S.; Brugge, Joan S.; Ahmed, Ahmed Ashour
Cell reports, 11/2023, Letnik: 42, Številka: 11Journal Article
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. Display omitted •Optimized conditions allow expansion of single FT cells into multi-lineage organoids•WNT/β-catenin pathway reporter captures rare multipotent organoid-forming stem cells•Fallopian tube (FT) stem cells are characterized with single-cell transcriptomics and mechanistic work•An estrogen-regulated WNT7A-FZD5 signaling axis maintains FT stem cells Progenitor fallopian tube cells are thought to initiate serous ovarian cancer, but their identification and characterization are lacking. Using optimized conditions to expand multi-lineage organoids from cells, Alsaadi et al. engineer reporter organoids to genetically tag, isolate, and characterize stem cells using mechanistic work and single-cell transcriptomics approaches.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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