Single-cell RNA sequencing of liver fine-needle aspirates captures immune diversity in the blood and liver in chronic hepatitis B patients-Reference-Cited by-同舟云学术

Single-cell RNA sequencing of liver fine-needle aspirates captures immune diversity in the blood and liver in chronic hepatitis B patients

Published:2023-05-10 Issue:5 Volume:78 Page:1525-1541
ISSN:0270-9139
Container-title:Hepatology
language:en
Short-container-title:

Author:

Genshaft Alex S.¹²³,Subudhi Sonu⁴^ORCID,Keo Arlin⁵⁶,Sanchez Vasquez Juan Diego⁷⁸,Conceição-Neto Nádia⁹,Mahamed Deeqa⁷,Boeijen Lauke L.⁵,Alatrakchi Nadia⁴,Oetheimer Chris⁴,Vilme Mike¹²³,Drake Riley¹²³,Fleming Ira¹²³,Tran Nancy¹²³,Tzouanas Constantine¹²³,Joseph-Chazan Jasmin¹²³¹⁰,Arreola Villanueva Martin¹²³¹¹,van de Werken Harmen J. G.⁵⁶¹²¹³,van Oord Gertine W.⁵,Groothuismink Zwier M. A.⁵,Beudeker Boris J.⁵,Osmani Zgjim⁵,Nkongolo Shirin⁷,Mehrotra Aman⁷,Spittaels Kurt⁹,Feld Jordan⁷^ORCID,Chung Raymond T.⁴,de Knegt Robert J.⁵,Janssen Harry L. A.⁵⁷,Aerssens Jeroen⁹^ORCID,Bollekens Jacques⁹,Hacohen Nir³¹⁰,Lauer Georg M.²^ORCID,Boonstra Andre⁵^ORCID,Shalek Alex K.¹²³^ORCID,Gehring Adam J.⁷⁸^ORCID

Affiliation:

1. Institute for Medical Engineering and Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Massachusetts, USA

2. The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, Massachusetts, USA

3. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

4. Liver Center, Division of Gastroenterology and Liver Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

5. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands

6. Cancer Computational Biology Center, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands

7. Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada

8. Department of Immunology, University of Toronto, Toronto, Ontario, Canada

9. Infectious Diseases Biomarkers, Janssen Research and Development, Beerse, Belgium

10. Department of Immunology, Harvard Medical School, Boston, Massachusetts, USA

11. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

12. Department of Urology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands

13. Department of Immunology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands

Abstract

Background and Aims: HBV infection is restricted to the liver, where it drives exhaustion of virus-specific T and B cells and pathogenesis through dysregulation of intrahepatic immunity. Our understanding of liver-specific events related to viral control and liver damage has relied almost solely on animal models, and we lack useable peripheral biomarkers to quantify intrahepatic immune activation beyond cytokine measurement. Our objective was to overcome the practical obstacles of liver sampling using fine-needle aspiration and develop an optimized workflow to comprehensively compare the blood and liver compartments within patients with chronic hepatitis B using single-cell RNA sequencing. Approach and Results: We developed a workflow that enabled multi-site international studies and centralized single-cell RNA sequencing. Blood and liver fine-needle aspirations were collected, and cellular and molecular captures were compared between the Seq-Well S3 picowell-based and the 10× Chromium reverse-emulsion droplet–based single-cell RNA sequencing technologies. Both technologies captured the cellular diversity of the liver, but Seq-Well S3 effectively captured neutrophils, which were absent in the 10× dataset. CD8 T cells and neutrophils displayed distinct transcriptional profiles between blood and liver. In addition, liver fine-needle aspirations captured a heterogeneous liver macrophage population. Comparison between untreated patients with chronic hepatitis B and patients treated with nucleoside analogs showed that myeloid cells were highly sensitive to environmental changes while lymphocytes displayed minimal differences. Conclusions: The ability to electively sample and intensively profile the immune landscape of the liver, and generate high-resolution data, will enable multi-site clinical studies to identify biomarkers for intrahepatic immune activity in HBV and beyond.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Hepatology

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