Important studies in 2021 demonstrated sophisticated developments in the study of liver fibrosis through omics. Cell-specific mapping, single-cell sequencing and deep-learning systems revealed complex intra-hepatic mechanisms and new computational platforms facilitating the research towards drug discovery in liver disease and in fibrosis.
Key advances
-
Cell-specific mapping of fibrosis-activated transcriptional networks controlling the pathogenic reprogramming of hepatocytes during the transition from nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) illuminates new mechanisms of fibrogenic crosstalk within the injured liver4.
-
The integration of single-cell RNA sequencing and flow cytometry studies identifies a subset of CD8+ tissue-resident memory T cells that attract and kill activated hepatic stellate cells via FAS–FAS ligand-mediated apoptosis during the resolution of NASH7.
-
The development of a new computational platform, called deep learning-based efficacy prediction system (DLEPS), exploits disease-specific gene signatures to predict new therapies for the treatment of chronic diseases, including NASH9.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Arthur, M. J. P. Reversibility of liver fibrosis and cirrhosis following treatment for hepatitis C. Gastroenterology 122, 1525–1528 (2002).
Fallowfield, J. A., Jimenez-Ramos, M. & Robertson, A. Emerging synthetic drugs for the treatment of liver cirrhosis. Expert Opin. Emerg. Drugs 26, 149–163 (2021).
Ramachandran, P. et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575, 512–518 (2019).
Loft, A. et al. Liver-fibrosis-activated transcriptional networks govern hepatocyte reprogramming and intra-hepatic communication. Cell Metab. 33, 1685–1700 (2021).
Higashi, T., Friedman, S. L. & Hoshida, Y. Hepatic stellate cells as key target in liver fibrosis. Adv. Drug Deliv. Rev. 121, 27–42 (2017).
Duffield, J. S. et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest. 115, 56–65 (2005).
Koda, Y. et al. CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells. Nat. Commun. 12, 4474 (2021).
Deczkowska, A. et al. XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis. Nat. Med. 27, 1043–1054 (2021).
Zhu, J. et al. Prediction of drug efficacy from transcriptional profiles with deep learning. Nat. Biotechnol. 39, 1444–1452 (2021).
Subramanian, A. et al. A next generation connectivity map: L1000 platform and the first 1,000,000 profiles. Cell 171, 1437–1452 (2017).
Acknowledgements
F.O. is supported by research grants from Medical Research Council (MR/K0019494/1 and MR/R023026/1).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
F.O. is a director, shareholder and employee of Fibrofind Ltd and a director and shareholder of FibroFind IP Ltd.
Rights and permissions
About this article
Cite this article
Oakley, F. Interrogating mechanisms of liver fibrosis with omics. Nat Rev Gastroenterol Hepatol 19, 89–90 (2022). https://doi.org/10.1038/s41575-021-00567-6
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41575-021-00567-6
