Spatiotemporal Single-Cell Analysis Reveals T Cell Clonal Dynamics and Phenotypic Plasticity in Human Graft-versus-Host Disease Article Swipe
Lingting Shi
,
Ajna Uzuni
,
Ximi K. Wang
,
Michael Pressler
,
David W Harle
,
Shami Chakrabarti
,
Rodney Macedo
,
Kirubel Belay
,
Christian Gordillo
,
Eric C. Raps
,
Jia Yi Zhang
,
Achille Nazaret
,
Joy Linyue Fan
,
Yinuo Jin
,
Xin Shen
,
Joshua Fuller
,
Tamjeed Azad
,
Jessie Huang
,
Pranik Chainani
,
Julian A. Abrams
,
Armando Del Portillo
,
Markus Y. Mapara
,
Mohamed Alhamar
,
Megan Sykes
,
José L. McFaline‐Figueroa
,
Elham Azizi
,
Ran Reshef
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.05.24.655962
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.05.24.655962
SUMMARY Allogeneic hematopoietic cell transplantation (alloHCT) is curative for various hematologic diseases but often leads to acute graft-versus-host disease (GVHD), a potentially life-threatening complication. We leverage GVHD as a uniquely tractable disease model to dissect complex T-cell–mediated pathology in 27 alloHCT recipients. We integrate pre-transplant identification of alloreactive T-cells with longitudinal tracking across blood and gut, using mixed lymphocyte reaction-based clonal “fingerprinting”, TCR clonotyping, single-cell RNA/TCR sequencing, and spatial transcriptomics. Using DecompTCR, a novel computational tool for longitudinal TCR analysis, we uncover clonal expansion programs linked to GVHD severity and TCR features. Multi-omics profiling of gut biopsies reveals enrichment and clonal expansion of CD8⁺ effector and ZNF683(Hobit)⁺ resident memory T-cells, cytolytic remodeling of regulatory and unconventional T-cells, and localization of CD8⁺ effector T-cells near intestinal stem cells in crypt loss regions. This framework defines dynamic immune circuit rewiring and phenotypic plasticity with implications for biomarkers and therapies. Graphical Abstract Highlights Persistent expansion of diverse alloreactive T cell clones is a hallmark of severe GVHD DecompTCR reveals dynamic clonal expansion programs linked to GVHD severity and clinical outcome CD8+ T cell clones exhibit phenotypic plasticity in vivo across intestinal tissue compartments in GVHD High-resolution spatial profiling shows CD8+ effector T cells localize near intestinal stem cell niches and drive epithelial injury in GVHD
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.05.24.655962
- https://www.biorxiv.org/content/biorxiv/early/2025/05/28/2025.05.24.655962.full.pdf
- OA Status
- green
- Cited By
- 2
- References
- 100
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410796793
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4410796793Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2025.05.24.655962Digital Object Identifier
- Title
-
Spatiotemporal Single-Cell Analysis Reveals T Cell Clonal Dynamics and Phenotypic Plasticity in Human Graft-versus-Host DiseaseWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-05-28Full publication date if available
- Authors
-
Lingting Shi, Ajna Uzuni, Ximi K. Wang, Michael Pressler, David W Harle, Shami Chakrabarti, Rodney Macedo, Kirubel Belay, Christian Gordillo, Eric C. Raps, Jia Yi Zhang, Achille Nazaret, Joy Linyue Fan, Yinuo Jin, Xin Shen, Joshua Fuller, Tamjeed Azad, Jessie Huang, Pranik Chainani, Julian A. Abrams, Armando Del Portillo, Markus Y. Mapara, Mohamed Alhamar, Megan Sykes, José L. McFaline‐Figueroa, Elham Azizi, Ran ReshefList of authors in order
- Landing page
-
https://doi.org/10.1101/2025.05.24.655962Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2025/05/28/2025.05.24.655962.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2025/05/28/2025.05.24.655962.full.pdfDirect OA link when available
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Phenotype, Host (biology), Dynamics (music), Biology, Phenotypic plasticity, Plasticity, Cell, Disease, Evolutionary biology, Genetics, Gene, Medicine, Psychology, Pathology, Thermodynamics, Physics, PedagogyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2Per-year citation counts (last 5 years)
- References (count)
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100Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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