Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repair
Summary: Pulmonary capillary endothelial cells (ECs) consist of two populations, CAP1 and CAP2; how each population reacts to diverse tissue injury is incompletely understood. Using single-cell multiome and mouse genetics, we characterize the induction and function of a truncated isoform of Ntrk2, N...
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Elsevier
2025-07-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225012349 |
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| author | Celine Shuet Lin Kong Mitheera V Jezreel Pantaleón-García Scott E. Evans Jichao Chen |
| author_facet | Celine Shuet Lin Kong Mitheera V Jezreel Pantaleón-García Scott E. Evans Jichao Chen |
| author_sort | Celine Shuet Lin Kong |
| collection | DOAJ |
| description | Summary: Pulmonary capillary endothelial cells (ECs) consist of two populations, CAP1 and CAP2; how each population reacts to diverse tissue injury is incompletely understood. Using single-cell multiome and mouse genetics, we characterize the induction and function of a truncated isoform of Ntrk2, Ntrk2-T1, in multiple lung injury models. Upon Sendai parainfluenza infection, Ntrk2-T1 is broadly induced in CAP1s after the initial interferon response, associated with increased intronic chromatin accessibility, and persists for weeks. Ntrk2-T1 ECs arise from CAP1s but not CAP2s—traced by KitCreER and Car4CreER, respectively—and proliferate and give rise to CAP1s but not CAP2s, as traced by Ntrk2CreER. Although also induced by lipopolysaccharide, H3N2 influenza, and COVID-19 injuries, EC-specific deletion of Ntrk2 has limited molecular and cellular consequences. Individuals with incident and prevalent respiratory diseases have lower plasma NTRK2. Our data identifies Ntrk2-T1 as an EC marker of lung injury-repair and enhances our understanding of EC heterogeneity. |
| format | Article |
| id | doaj-art-b5df10c77f524e61ba5178f514be22df |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-b5df10c77f524e61ba5178f514be22df2025-08-20T03:34:10ZengElsevieriScience2589-00422025-07-0128711297310.1016/j.isci.2025.112973Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repairCeline Shuet Lin Kong0Mitheera V1Jezreel Pantaleón-García2Scott E. Evans3Jichao Chen4Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USAThe University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA; Department of Genetics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pediatrics, Perinatal Institute Division of Pulmonary Biology, University of Cincinnati and Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; Corresponding authorSummary: Pulmonary capillary endothelial cells (ECs) consist of two populations, CAP1 and CAP2; how each population reacts to diverse tissue injury is incompletely understood. Using single-cell multiome and mouse genetics, we characterize the induction and function of a truncated isoform of Ntrk2, Ntrk2-T1, in multiple lung injury models. Upon Sendai parainfluenza infection, Ntrk2-T1 is broadly induced in CAP1s after the initial interferon response, associated with increased intronic chromatin accessibility, and persists for weeks. Ntrk2-T1 ECs arise from CAP1s but not CAP2s—traced by KitCreER and Car4CreER, respectively—and proliferate and give rise to CAP1s but not CAP2s, as traced by Ntrk2CreER. Although also induced by lipopolysaccharide, H3N2 influenza, and COVID-19 injuries, EC-specific deletion of Ntrk2 has limited molecular and cellular consequences. Individuals with incident and prevalent respiratory diseases have lower plasma NTRK2. Our data identifies Ntrk2-T1 as an EC marker of lung injury-repair and enhances our understanding of EC heterogeneity.http://www.sciencedirect.com/science/article/pii/S2589004225012349BiochemistryMolecular physiologyCell biology |
| spellingShingle | Celine Shuet Lin Kong Mitheera V Jezreel Pantaleón-García Scott E. Evans Jichao Chen Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repair iScience Biochemistry Molecular physiology Cell biology |
| title | Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repair |
| title_full | Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repair |
| title_fullStr | Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repair |
| title_full_unstemmed | Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repair |
| title_short | Truncated NTRK2 is induced in CAP1 endothelial cells during mouse lung injury-repair |
| title_sort | truncated ntrk2 is induced in cap1 endothelial cells during mouse lung injury repair |
| topic | Biochemistry Molecular physiology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225012349 |
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