Single-cell transcriptomics identifies a WNT7A-FZD5 signaling axis that maintains fallopian tube stem cells in patient-derived organoids.

Female Humans beta Catenin / metabolism Fallopian Tubes / metabolism Transcriptome / genetics Stem Cells / metabolism Wnt Signaling Pathway Organoids / metabolism Wnt Proteins / genetics Frizzled Receptors / metabolism
CP: Stem cell research ECM WNT estrogen fallopian tube organoids ovarian cancer single-cell RNA sequencing stem cells

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
28 Nov 2023
Historique:
received: 04 04 2023
revised: 31 07 2023
accepted: 11 10 2023
medline: 4 12 2023
pubmed: 2 11 2023
entrez: 2 11 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2023.113354 PMID: 37917586
pubmed: 37917586
pii: S2211-1247(23)01366-9
doi: 10.1016/j.celrep.2023.113354
pii:
doi:

Substances chimiques

beta Catenin 0
WNT7A protein, human 0
Wnt Proteins 0
FZD5 protein, human 0
Frizzled Receptors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113354

Informations de copyright

Copyright © 2023. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Abdulkhaliq 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.

Mara 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 Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

Zhiyuan 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 Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

Nina 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 Hospitals, Oxford OX3 7LE, UK.

Matteo 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 Hospitals, Oxford OX3 7LE, UK.

Laura Santana 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.

Moiad Alazzam (M)

Department of Gynecological Oncology, Churchill Hospital, Oxford University Hospitals, Oxford OX3 7LE, UK.

Jason Jiang (J)

Department of Gynecological Oncology, Churchill Hospital, Oxford University Hospitals, Oxford OX3 7LE, UK.

Beena Abdul (B)

Department of Gynecological Oncology, Churchill Hospital, Oxford University Hospitals, Oxford OX3 7LE, UK.

Hooman Soleymani Majd (H)

Medical Sciences Division, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.

Levi L Blazer (LL)

School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.

Jarret Adams (J)

School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.

Francesca Silvestri (F)

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Sachdev S Sidhu (SS)

School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.

Joan S Brugge (JS)

Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Boston, MA, USA.

Ahmed Ashour 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 Hospitals, Oxford OX3 7LE, UK. Electronic address: ahmed.ahmed@wrh.ox.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Single-cell transcriptomics identifies a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Single-cell transcriptomics identifies a...
questionsmedicales.fr › Structures anatomiques de l'animal › Oviductes › Trompes utérines › Single-cell transcriptomics identifies a...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Single-cell transcriptomics identifies a...
questionsmedicales.fr › Cellules › Cellules souches › Single-cell transcriptomics identifies a...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › Single-cell transcriptomics identifies a...
questionsmedicales.fr › Tissus › Organoïdes › Single-cell transcriptomics identifies a...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de type Wingless › Single-cell transcriptomics identifies a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs Wnt › Récepteurs Frizzled › Single-cell transcriptomics identifies a...