دورية أكاديمية
Organoid modeling of human fetal lung alveolar development reveals mechanisms of cell fate patterning and neonatal respiratory disease.
| العنوان: | Organoid modeling of human fetal lung alveolar development reveals mechanisms of cell fate patterning and neonatal respiratory disease. |
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| المؤلفون: | Lim K; Wellcome Trust, CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK; Wellcome Trust, MRC Stem Cell Institute, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK., Donovan APA; Wellcome Trust, CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK., Tang W; Wellcome Trust, CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK; Wellcome Trust, MRC Stem Cell Institute, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK., Sun D; Wellcome Trust, CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK; Wellcome Trust, MRC Stem Cell Institute, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK., He P; Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK., Pett JP; Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK., Teichmann SA; Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK., Marioni JC; Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK., Meyer KB; Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK., Brand AH; Wellcome Trust, CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK., Rawlins EL; Wellcome Trust, CRUK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK; Wellcome Trust, MRC Stem Cell Institute, Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK. Electronic address: elr21@cam.ac.uk. |
| المصدر: | Cell stem cell [Cell Stem Cell] 2023 Jan 05; Vol. 30 (1), pp. 20-37.e9. Date of Electronic Publication: 2022 Dec 08. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101311472 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-9777 (Electronic) Linking ISSN: 18759777 NLM ISO Abbreviation: Cell Stem Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, MA : Cell Press |
| مواضيع طبية MeSH: | Cell Differentiation*/physiology , Lung*/embryology , Organoids*, Humans ; Infant, Newborn ; Alveolar Epithelial Cells/metabolism ; Cell Lineage ; Respiratory Tract Diseases/embryology ; Respiratory Tract Diseases/metabolism |
| مستخلص: | Variation in lung alveolar development is strongly linked to disease susceptibility. However, underlying cellular and molecular mechanisms are difficult to study in humans. We have identified an alveolar-fated epithelial progenitor in human fetal lungs, which we grow as self-organizing organoids that model key aspects of cell lineage commitment. Using this system, we have functionally validated cell-cell interactions in the developing human alveolar niche, showing that Wnt signaling from differentiating fibroblasts promotes alveolar-type-2 cell identity, whereas myofibroblasts secrete the Wnt inhibitor, NOTUM, providing spatial patterning. We identify a Wnt-NKX2.1 axis controlling alveolar differentiation. Moreover, we show that differential binding of NKX2.1 coordinates alveolar maturation, allowing us to model the effects of human genetic variation in NKX2.1 on alveolar differentiation. Our organoid system recapitulates key aspects of human fetal lung stem cell biology allowing mechanistic experiments to determine the cellular and molecular regulation of human development and disease. Competing Interests: Declaration of interests S.A.T. is a member of the scientific advisory board for the following companies: Biogen, Foresite Labs, GSK, Qiagen, CRG Barcelona, Jax Labs, SciLife Lab, and Allen Institute. She is a consultant for Genentech and Roche. She is co-founder of Transition Bio and a member of the Board. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Cell Stem Cell. 2023 Jan 5;30(1):5-6. (PMID: 36608678) |
| معلومات مُعتمدة: | MR/P009581/1 United Kingdom Medical Research Council; MR/S035907/1 United Kingdom Medical Research Council; 109146/Z/15/Z United Kingdom Wellcome Trust; 203144/Z/16/Z United Kingdom Wellcome Trust; C6946/A24843 United Kingdom Cancer Research UK |
| فهرسة مساهمة: | Keywords: NKX2.1; NOTUM; WNT; alveolar differentiation; alveolar patterning; distal tip; human lung development; organoids; stem cell |
| تواريخ الأحداث: | Date Created: 20221209 Date Completed: 20230208 Latest Revision: 20230213 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.stem.2022.11.013 |
| PMID: | 36493780 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1875-9777 |
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| DOI: | 10.1016/j.stem.2022.11.013 |