Spatial landscape of pretransplant liver disease and post-transplant immune outcomes in children

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Abstract
Defining molecular patterns underlying pediatric end-stage liver disease and its treatment with liver transplantation requires rich datasets spanning a multitude of diagnoses and transplant outcomes. Here, we describe the spatial molecular landscape of approximately five million liver cell profiles from 98 liver tissue samples. The samples span donor liver, used here as a reference tissue, and end-stage diseases including biliary atresia, progressive familial intrahepatic cholestasis, hepatoblastoma, acute liver failure, and gestational alloimmune liver disease. Post-transplant liver allograft biopsies include those without and with T-cell-mediated and antibody-mediated rejection, mixed pathology, and outcome groups from immunosuppression withdrawal studies. Samples were profiled using the CosMx Human Universal Cell Characterization RNA Panel (1K) and the CosMx Human 6K Discovery Panel (6K). Preliminary exploratory analyses include cellular composition and gene abundance and variability across clinical cohorts. A twelve-gene signature comprising the genes with the highest variance implicates acute-phase response genes (e.g., SAA1 ) and profibrotic genes (e.g., COL1A1 ) as a shared link across these otherwise distinct conditions. This injury-repair-remodeling gene network warrants further investigation through higher-resolution, zone-specific spatial mapping to help clarify disease pathogenesis.
Funding Information
  • Raizman-Haney Endowment–RS; Hillman Foundation of Pittsburgh; Szalay Family Foundation; Janet Family; Pediatric Surgery Scientific Program.

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