RT Journal Article
SR Electronic
T1 Clinical implementation of single-cell RNA sequencing using liver fine needle aspirate tissue sampling and centralized processing captures compartment specific immuno-diversity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.30.470634
DO 10.1101/2021.11.30.470634
A1 Alex S. Genshaft
A1 Sonu Subudhi
A1 Arlin Keo
A1 Juan D. Sanchez Vasquez
A1 Nádia Conceição-Neto
A1 Deeqa Mahamed
A1 Lauke L. Boeijen
A1 Nadia Alatrakchi
A1 Chris Oetheimer
A1 Mike Vilme
A1 Riley Drake
A1 Ira Fleming
A1 Nancy Tran
A1 Constantine Tzouanas
A1 Jasmin Joseph-Chazan
A1 Martin Arreola Villanueva
A1 Harmen J. G. van de Werken
A1 Gertine W. van Oord
A1 Zwier M.A. Groothuismink
A1 Boris J. Beudeker
A1 Zgjim Osmani
A1 Shirin Nkongolo
A1 Aman Mehrotra
A1 Jordan Feld
A1 Raymond T. Chung
A1 Robert J. de Knegt
A1 Harry L. A. Janssen
A1 Jeroen Aerssens
A1 Jacques Bollekens
A1 Nir Hacohen
A1 Georg M. Lauer
A1 Andre Boonstra
A1 Alex K. Shalek
A1 Adam Gehring
YR 2021
UL http://biorxiv.org/content/early/2021/12/02/2021.11.30.470634.abstract
AB 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.Competing Interest StatementN.C.N., J.A., and J.B. are employees of Janssen Pharmaceutical NV. N.H. holds equity in BioNTech and is a consultant for Related Sciences. J.F., R.J.D.K, and H.L.A.J., receive funding from AbbVie. J.F. and H.L.A.J. receive funding from Arbutus. J.F., R.J.D.K., H.L.A.J., A.B., and A.G. receive funding from Gilead Sciences. J.F., R.J.D.K., H.L.A.J., G.M.L., A.B., and A.G. receive funding from Janssen Pharmaceutical. J.F. receives funding from Eiger and Enanta. R.J.D.K. receives funding from BMS, Medtronic, Philips. H.L.A.J. receives funding from Merck, Myers-Squibb and Bristol. A.B. receives funding from Fujirebio. R.J.D.K. and H.L.A.J. receive funding from Roche. A.B. and A.G. receive funding from GSK. J.F. and R.J.D.K. report compensation for consulting from AbbVie. J.F., R.J.D.K., and H.L.A.J. report compensation for consulting from Gilead Sciences. J.F. and H.L.A.J. report compensation for consulting from Arbutus. J.F., H.L.A.J., and A.G. report compensation for consulting from GSK. R.J.D.K., H.L.A.J., and A.G. report compensation for consulting from Janssen Pharmaceutical and Roche. R.J.D.K., H.L.A.J., and A.K.S. report compensation for consulting from Merck/ Schering Plough. H.L.A.J., and A.G. report compensation for consulting from Vir Biotechnology Inc. R.J.D.K. reports compensation for consulting from BMS, Echosens, Medtronic and Norgine. H.L.A.J. reports compensation for consulting from Aligos, Arena, Eiger, Enyo, Regulus, VBI Vaccines and Viroclinics. A.K.S. reports compensation for consulting from Honeycomb Biotechnologies, Cellarity, Repertoire Immune Medicines, Ochre Bio, Third Rock Ventures, Hovione, Relation Therapeutics, FL82, and Dahlia Biosciences. A.G. reports compensation for consulting from Finch Therapeutics and SQZ BioTech. The other authors declare no competing interests.