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. |
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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 |
تدمد: | 1558-8238 |
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DOI: | 10.1172/JCI147343 |