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Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids.
Gerli, Mattia Francesco Maria; Calà, Giuseppe; Beesley, Max Arran; Sina, Beatrice; Tullie, Lucinda; Sun, Kylin Yunyan; Panariello, Francesco; Michielin, Federica; Davidson, Joseph R; Russo, Francesca Maria; Jones, Brendan C; Lee, Dani Do Hyang; Savvidis, Savvas; Xenakis, Theodoros; Simcock, Ian C; Straatman-Iwanowska, Anna A; Hirst, Robert A; David, Anna L; O'Callaghan, Christopher; Olivo, Alessandro; Eaton, Simon; Loukogeorgakis, Stavros P; Cacchiarelli, Davide; Deprest, Jan; Li, Vivian S W; Giobbe, Giovanni Giuseppe; De Coppi, Paolo.
Affiliation
  • Gerli MFM; Department of Surgical Biotechnology, Division of Surgery and Interventional Science, University College London, London, UK. m.gerli@ucl.ac.uk.
  • Calà G; Great Ormond Street Institute of Child Health, University College London, London, UK. m.gerli@ucl.ac.uk.
  • Beesley MA; Department of Surgical Biotechnology, Division of Surgery and Interventional Science, University College London, London, UK.
  • Sina B; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Tullie L; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Sun KY; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Panariello F; Politecnico di Milano, Milan, Italy.
  • Michielin F; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Davidson JR; Stem Cell and Cancer Biology Laboratory, The Francis Crick Institute, London, UK.
  • Russo FM; Department of Surgical Biotechnology, Division of Surgery and Interventional Science, University College London, London, UK.
  • Jones BC; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Lee DDH; Armenise/Harvard Laboratory of Integrative Genomics, Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
  • Savvidis S; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Xenakis T; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Simcock IC; Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK.
  • Straatman-Iwanowska AA; Department of Development and Regeneration, Woman and Child and UZ Leuven Clinical Department of Obstetrics and Gynaecology, KU Leuven, Leuven, Belgium.
  • Hirst RA; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • David AL; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • O'Callaghan C; Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
  • Olivo A; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Eaton S; Great Ormond Street Institute of Child Health, University College London, London, UK.
  • Loukogeorgakis SP; Department of Radiology, Great Ormond Street Hospital, London, UK.
  • Cacchiarelli D; Department of Respiratory Sciences, University of Leicester, Leicester, UK.
  • Deprest J; Department of Respiratory Sciences, University of Leicester, Leicester, UK.
  • Li VSW; Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK.
  • Giobbe GG; Department of Development and Regeneration, Woman and Child and UZ Leuven Clinical Department of Obstetrics and Gynaecology, KU Leuven, Leuven, Belgium.
  • De Coppi P; Great Ormond Street Institute of Child Health, University College London, London, UK.
Nat Med ; 30(3): 875-887, 2024 Mar.
Article in En | MEDLINE | ID: mdl-38438734
ABSTRACT
Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous. Amniotic fluid (AF) is a source of cells from multiple developing organs. Using single-cell analysis, we characterized the cellular identities present in human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modeling, we derived lung organoids from AF and tracheal fluid cells of congenital diaphragmatic hernia fetuses, recapitulating some features of the disease. AF organoids are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalized to the fetus at clinically relevant developmental stages.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hernias, Diaphragmatic, Congenital Limits: Female / Humans / Pregnancy Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2024 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hernias, Diaphragmatic, Congenital Limits: Female / Humans / Pregnancy Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2024 Document type: Article Affiliation country: