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Single-cell transcriptomics identifies a WNT7A-FZD5 signaling axis that maintains fallopian tube stem cells in patient-derived organoids.
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.
Affiliation
  • Alsaadi A; Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK.
  • Artibani M; Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK; Gene Regulatory Networks in Development and Disease Laboratory, MRC Weatherall
  • Hu Z; Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK; Gene Regulatory Networks in Development and Disease Laboratory, MRC Weatherall
  • Wietek N; Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK; Department of Gynecological Oncology, Churchill Hospital, Oxford University Ho
  • Morotti M; Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK; Department of Gynecological Oncology, Churchill Hospital, Oxford University Ho
  • Gonzalez LS; Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK.
  • Alazzam M; Department of Gynecological Oncology, Churchill Hospital, Oxford University Hospitals, Oxford OX3 7LE, UK.
  • Jiang J; Department of Gynecological Oncology, Churchill Hospital, Oxford University Hospitals, Oxford OX3 7LE, UK.
  • Abdul B; Department of Gynecological Oncology, Churchill Hospital, Oxford University Hospitals, Oxford OX3 7LE, UK.
  • Soleymani Majd H; Medical Sciences Division, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Blazer LL; School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
  • Adams J; School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
  • Silvestri F; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Sidhu SS; School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
  • Brugge JS; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Boston, MA, USA.
  • Ahmed AA; Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford OX3 9DU, UK; Department of Gynecological Oncology, Churchill Hospital, Oxford University Ho
Cell Rep ; 42(11): 113354, 2023 11 28.
Article in En | MEDLINE | ID: mdl-37917586
ABSTRACT
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/ß-catenin signaling and engineer endogenous WNT/ß-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/ß-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Beta Catenin / Fallopian Tubes Limits: Female / Humans Language: En Journal: Cell Rep Year: 2023 Type: Article Affiliation country: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Beta Catenin / Fallopian Tubes Limits: Female / Humans Language: En Journal: Cell Rep Year: 2023 Type: Article Affiliation country: United kingdom