Academic Journal
Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease.
| Τίτλος: | Spatiotemporal single-cell profiling reveals T cell clonal dynamics and phenotypic plasticity in human graft-versus-host disease. |
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| Συγγραφείς: | Shi L; Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Uzuni A; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., Wang XK; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., Pressler M; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Harle DW; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.; Columbia Institute of Human Nutrition, Columbia University, New York, NY, USA., Chakrabarti S; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., Macedo R; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., Belay K; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA., Gordillo CA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., McMahon-Skates T; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., Raps E; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA., Zhang JYA; Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Nazaret A; Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.; Department of Computer Science, Columbia University, New York, NY, USA., Fan JL; Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Jin Y; Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Shen X; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Fuller JS; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Azad T; Department of Computer Science, Columbia University, New York, NY, USA., Huang J; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Chainani P; Department Statistics and Data Science, Yale University, New Haven, CT, USA., Nima JP; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Abrams JA; Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, Columbia University, New York, NY, USA., Del Portillo A; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, Columbia University, New York, NY, USA., Mapara MY; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., Alhamar M; Department of Pathology and Laboratory Medicine, Henry Ford Health, Detroit, MI, USA., Sykes M; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA., McFaline-Figueroa JL; Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Azizi E; Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA. elham@azizilab.com.; Department of Biomedical Engineering, Columbia University, New York, NY, USA. elham@azizilab.com.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA. elham@azizilab.com.; Department of Computer Science, Columbia University, New York, NY, USA. elham@azizilab.com.; Data Science Institute, Columbia University, New York, NY, USA. elham@azizilab.com., Reshef R; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA. ran.reshef@columbia.edu.; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA. ran.reshef@columbia.edu. |
| Πηγή: | Nature immunology [Nat Immunol] 2026 Oct; Vol. 27 (10), pp. 2156-2171. Date of Electronic Publication: 2026 Sep 17. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, NY : Nature America Inc. c2000- |
| Ιατρικοί όροι (MeSH): | Graft vs Host Disease*/immunology , Graft vs Host Disease*/genetics , Hematopoietic Stem Cell Transplantation*/adverse effects , CD8-Positive T-Lymphocytes*/immunology , Memory T Cells*/immunology , Cell Plasticity*/immunology, Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Clone Cells/immunology ; Humans ; Single-Cell Analysis ; Female ; Phenotype ; Male ; Adult ; Middle Aged ; Single-Cell Gene Expression Analysis ; Spatial Transcriptomics ; Immunologic Memory |
| Περίληψη: | Allogeneic hematopoietic cell transplantation cures hematologic diseases but is limited by acute graft‑versus‑host disease. How human T cell clones drive epithelial injury remains poorly mapped. We studied 31 transplant recipients, integrating longitudinal T cell antigen receptor (TCR) profiling with single-cell RNA sequencing/TCR sequencing and spatial transcriptomics to track T cell clonal dynamics. We developed DecompTCR to resolve temporal dynamics and adapted computational tools to map clone phenotypes and niches in tissue. Our analyses revealed that cyclophosphamide selectively depletes alloreactive clones, although insufficient early expansion leads to incomplete depletion and severe disease. Severe graft‑versus‑host disease is marked by persistent expansion of alloreactive clones, rewiring of homeostatic cell types and diversification of donor-derived CD8+ clonotypes that acquire Hobit (ZNF683)+ tissue‑resident memory T (T (© 2026. Springer Nature America, Inc.) |
| Competing Interests: | Competing interests: R.R. reports consulting or advisory roles with Allogene, Autolus, Bayer, CareDx, Gilead Sciences, Orca Bio, Pierre Fabre Pharmaceuticals, Sail Biomedicines, Sana Biotechnology, Sanofi and TScan, and research funding from AbbVie, Allogene, Arcellx, AstraZeneca, BMS, Cabaletta, CareDx, Gilead Sciences, Imugene, J&J, Kinomica, Sanofi, Sonoma Bio, Synthekine, TScan and Vittoria Therapeutics. The other authors declare no competing interests. |
| Σχόλια: | Update of: bioRxiv. 2025 May 28:2025.05.24.655962. doi: 10.1101/2025.05.24.655962.. (PMID: 40501545) |
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| Grant Information: | R00CA230195 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); GG016982 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); R01HG012875 U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI); R35HG011941 U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI); CBET 2146007 National Science Foundation (NSF) |
| Substance Nomenclature: | 0 (Receptors, Antigen, T-Cell) |
| Entry Date(s): | Date Created: 20260917 Date Completed: 20261002 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1038/s41590-026-02631-2 |
| PMID: | 42754741 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1529-2916 |
|---|---|
| DOI: | 10.1038/s41590-026-02631-2 |