Clinical implementation of single-cell RNA sequencing using liver fine needle aspirate tissue sampling and centralized processing captures compartment specific immuno-diversity
Genshaft, A. S.; Subudhi, S.; Keo, A.; Sanchez Vasquez, J. D.; Conceicao-Neto, N.; Mahamed, D.; Boeijen, L. L.; Alatrakchi, N.; Oetheimer, C.; Vilme, M.; Drake, R.; Fleming, I.; Tran, N.; Tzouanas, C.; Joseph-Chazan, J.; Villanueva, M. A.; van de Werken, H. J. G.; van Oord, G. W.; Groothuismink, Z. M. A.; Beudeker, B. J.; Osmani, Z.; Nkongolo, S.; Mehrotra, A.; Feld, J.; Chung, R. T.; de Knegt, R. J.; Janssen, H. L. A.; Aerssens, J.; Bollekens, J.; Hacohen, N.; Lauer, G. M.; Boonstra, A.; Shalek, A. K.; Gehring, A.
Show abstract
Blood samples are frequently collected in human studies of the immune system but poorly represent tissue-resident immunity. Understanding the immunopathogenesis of tissue-restricted diseases, such as chronic hepatitis B, necessitates direct investigation of local immune responses. We developed a workflow that enables frequent, minimally invasive collection of liver fine-needle aspirates in multi-site international studies and centralized single-cell RNA sequencing data generation using the Seq-Well S3 picowell-based technology. All immunological cell types were captured, including liver macrophages, and showed distinct compartmentalization and transcriptional profiles, providing a systematic assessment of the capabilities and limitations of peripheral blood samples when investigating tissue-restricted diseases. The ability to electively sample the liver of chronic viral hepatitis patients and generate high-resolution data will enable multi-site clinical studies to power fundamental and therapeutic discovery.
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