دورية أكاديمية
Transcription factor FOXF1 identifies compartmentally distinct mesenchymal cells with a role in lung allograft fibrogenesis.
| العنوان: | Transcription factor FOXF1 identifies compartmentally distinct mesenchymal cells with a role in lung allograft fibrogenesis. |
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| المؤلفون: | Braeuer RR; Department of Internal Medicine., Walker NM; Department of Internal Medicine., Misumi K; Department of Internal Medicine., Mazzoni-Putman S; Department of Internal Medicine., Aoki Y; Department of Internal Medicine., Liao R; Department of Computational Medicine and Bioinformatics., Vittal R; Department of Internal Medicine., Kleer GG; Department of Internal Medicine., Wheeler DS; Department of Internal Medicine., Sexton JZ; Department of Pharmacy., Farver CF; Department of Pathology, and., Welch JD; Department of Computational Medicine and Bioinformatics.; Department of Computer Science and Engineering, University of Michigan, Ann Arbor, Michigan, USA., Lama VN; Department of Internal Medicine. |
| المصدر: | The Journal of clinical investigation [J Clin Invest] 2021 Nov 01; Vol. 131 (21). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation Original Publication: New Haven [etc.] American Society for Clinical Investigation. |
| مواضيع طبية MeSH: | Lung Transplantation*, Forkhead Transcription Factors/*metabolism , Graft Rejection/*metabolism , Mesenchymal Stem Cells/*metabolism , Pulmonary Alveoli/*metabolism , Pulmonary Fibrosis/*metabolism, Allografts ; Animals ; Chronic Disease ; Forkhead Transcription Factors/genetics ; Graft Rejection/genetics ; Graft Rejection/pathology ; Mesenchymal Stem Cells/pathology ; Mice ; Mice, Transgenic ; Pulmonary Alveoli/pathology ; Pulmonary Fibrosis/etiology ; Pulmonary Fibrosis/genetics ; Pulmonary Fibrosis/pathology |
| مستخلص: | In this study, we demonstrate that forkhead box F1 (FOXF1), a mesenchymal transcriptional factor essential for lung development, was retained in a topographically distinct mesenchymal stromal cell population along the bronchovascular space in an adult lung and identify this distinct subset of collagen-expressing cells as key players in lung allograft remodeling and fibrosis. Using Foxf1-tdTomato BAC (Foxf1-tdTomato) and Foxf1-tdTomato Col1a1-GFP mice, we show that Lin-Foxf1+ cells encompassed the stem cell antigen 1+CD34+ (Sca1+CD34+) subset of collagen 1-expressing mesenchymal cells (MCs) with a capacity to generate CFU and lung epithelial organoids. Histologically, FOXF1-expressing MCs formed a 3D network along the conducting airways; FOXF1 was noted to be conspicuously absent in MCs in the alveolar compartment. Bulk and single-cell RNA-Seq confirmed distinct transcriptional signatures of Foxf1+ and Foxf1- MCs, with Foxf1-expressing cells delineated by their high expression of the transcription factor glioma-associated oncogene 1 (Gli1) and low expression of integrin α8 (Itga), versus other collagen-expressing MCs. FOXF1+Gli1+ MCs showed proximity to Sonic hedgehog-expressing (Shh-expressing) bronchial epithelium, and mesenchymal expression of Foxf1 and Gli1 was found to be dependent on paracrine Shh signaling in epithelial organoids. Using a murine lung transplant model, we show dysregulation of epithelial-mesenchymal SHH/GLI1/FOXF1 crosstalk and expansion of this specific peribronchial MC population in chronically rejecting fibrotic lung allografts. |
| References: | Nat Commun. 2020 Apr 21;11(1):1920. (PMID: 32317643) Am J Pathol. 2011 Jun;178(6):2461-9. (PMID: 21641374) Nature. 2015 Oct 22;526(7574):578-82. (PMID: 26436454) Sci Rep. 2020 Dec 4;10(1):21231. (PMID: 33277571) Cell. 2017 Sep 7;170(6):1134-1148.e10. (PMID: 28886382) Am J Respir Crit Care Med. 2011 Apr 15;183(8):1062-70. (PMID: 21169468) JCI Insight. 2020 Dec 3;5(23):. (PMID: 33268593) Stem Cells. 2009 Mar;27(3):623-33. (PMID: 19074419) J Clin Invest. 2007 Apr;117(4):989-96. (PMID: 17347686) J Clin Invest. 2017 Apr 3;127(4):1517-1530. (PMID: 28240604) Cell Rep. 2018 Mar 27;22(13):3625-3640. (PMID: 29590628) Am J Respir Cell Mol Biol. 1999 Dec;21(6):655-7. (PMID: 10572061) Circ Res. 2014 Sep 26;115(8):709-20. (PMID: 25091710) J Biol Chem. 2009 Feb 27;284(9):5936-44. (PMID: 19049965) Mech Dev. 1997 Dec;69(1-2):53-69. (PMID: 9486531) Development. 2001 Jun;128(12):2397-406. (PMID: 11493558) |
| معلومات مُعتمدة: | R01 HL094622 United States HL NHLBI NIH HHS; R01 HL118017 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: Adult stem cells; Cell Biology; Fibrosis; Organ transplantation; Pulmonology |
| المشرفين على المادة: | 0 (Forkhead Transcription Factors) 0 (Foxf1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20210921 Date Completed: 20211207 Latest Revision: 20220202 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8553552 |
| DOI: | 10.1172/JCI147343 |
| PMID: | 34546975 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1558-8238 |
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| DOI: | 10.1172/JCI147343 |