A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver
- Author
- Andrew S. Perry, Niran Hadad, Emeli Chatterjee, Maria Jimenez-Ramos, Eric Farber-Eger, Rashedeh Roshani, Lindsey K. Stolze, Michael J. Betti, Shilin Zhao, Shi Huang, Liesbet Martens (UGent) , Timothy J. Kendall, Tinne Thoné (UGent) , Kaushik Amancherla, Samuel Bailin, Curtis L. Gabriel, John Koethe, J. Jeffrey Carr, James Greg Terry, Nataraja Sarma Vaitinadin, Jane E. Freedman, Kahraman Tanriverdi, Eric Alsop, Kendall Van Keuren-Jensen, John F.K. Sauld, Gautam Mahajan, Sadiya S. Khan, Laura Colangelo, Matthew Nayor, Susan Fisher-Hoch, Joseph B. McCormick, Kari E. North, Jennifer E. Below, Quinn S. Wells, E. Dale Abel, Ravi Kalhan, Charlotte Scott (UGent) , Martin Guilliams (UGent) , Eric R. Gamazon, Jonathan A. Fallowfield, Nicholas E. Banovich, Saumya Das and Ravi Shah
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- Project
- Abstract
- Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver. These transcripts are differentially expressed across areas of steatosis in spatial transcriptomics, and several are dynamic during stages of steatosis. Circulating multi-protein signatures of steatosis strongly associate with fatty liver disease and multi-system metabolic outcomes. Using a humanized "liver-on-a-chip" model, we induce hepatic steatosis, confirming cell-specific expression of prioritized targets. These results underscore the utility of this approach to identify a prognostic, functional, dynamic "liquid biopsy" of human liver, relevant to biomarker discovery and mechanistic research applications.
- Keywords
- NONALCOHOLIC STEATOHEPATITIS, YOUNG-ADULTS, DISEASE, NASH, SUSCEPTIBILITY, HEPATOCYTES, HOMEOSTASIS, INDUCTION, BIOMARKER, HEALTH
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JGY24HNCS3WN79AA8X6XDFRV
- MLA
- Perry, Andrew S., et al. “A Prognostic Molecular Signature of Hepatic Steatosis Is Spatially Heterogeneous and Dynamic in Human Liver.” CELL REPORTS MEDICINE, vol. 5, no. 12, 2024, doi:10.1016/j.xcrm.2024.101871.
- APA
- Perry, A. S., Hadad, N., Chatterjee, E., Jimenez-Ramos, M., Farber-Eger, E., Roshani, R., … Shah, R. (2024). A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver. CELL REPORTS MEDICINE, 5(12). https://doi.org/10.1016/j.xcrm.2024.101871
- Chicago author-date
- Perry, Andrew S., Niran Hadad, Emeli Chatterjee, Maria Jimenez-Ramos, Eric Farber-Eger, Rashedeh Roshani, Lindsey K. Stolze, et al. 2024. “A Prognostic Molecular Signature of Hepatic Steatosis Is Spatially Heterogeneous and Dynamic in Human Liver.” CELL REPORTS MEDICINE 5 (12). https://doi.org/10.1016/j.xcrm.2024.101871.
- Chicago author-date (all authors)
- Perry, Andrew S., Niran Hadad, Emeli Chatterjee, Maria Jimenez-Ramos, Eric Farber-Eger, Rashedeh Roshani, Lindsey K. Stolze, Michael J. Betti, Shilin Zhao, Shi Huang, Liesbet Martens, Timothy J. Kendall, Tinne Thoné, Kaushik Amancherla, Samuel Bailin, Curtis L. Gabriel, John Koethe, J. Jeffrey Carr, James Greg Terry, Nataraja Sarma Vaitinadin, Jane E. Freedman, Kahraman Tanriverdi, Eric Alsop, Kendall Van Keuren-Jensen, John F.K. Sauld, Gautam Mahajan, Sadiya S. Khan, Laura Colangelo, Matthew Nayor, Susan Fisher-Hoch, Joseph B. McCormick, Kari E. North, Jennifer E. Below, Quinn S. Wells, E. Dale Abel, Ravi Kalhan, Charlotte Scott, Martin Guilliams, Eric R. Gamazon, Jonathan A. Fallowfield, Nicholas E. Banovich, Saumya Das, and Ravi Shah. 2024. “A Prognostic Molecular Signature of Hepatic Steatosis Is Spatially Heterogeneous and Dynamic in Human Liver.” CELL REPORTS MEDICINE 5 (12). doi:10.1016/j.xcrm.2024.101871.
- Vancouver
- 1.Perry AS, Hadad N, Chatterjee E, Jimenez-Ramos M, Farber-Eger E, Roshani R, et al. A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver. CELL REPORTS MEDICINE. 2024;5(12).
- IEEE
- [1]A. S. Perry et al., “A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver,” CELL REPORTS MEDICINE, vol. 5, no. 12, 2024.
@article{01JGY24HNCS3WN79AA8X6XDFRV,
abstract = {{Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver. These transcripts are differentially expressed across areas of steatosis in spatial transcriptomics, and several are dynamic during stages of steatosis. Circulating multi-protein signatures of steatosis strongly associate with fatty liver disease and multi-system metabolic outcomes. Using a humanized "liver-on-a-chip" model, we induce hepatic steatosis, confirming cell-specific expression of prioritized targets. These results underscore the utility of this approach to identify a prognostic, functional, dynamic "liquid biopsy" of human liver, relevant to biomarker discovery and mechanistic research applications.}},
articleno = {{101871}},
author = {{Perry, Andrew S. and Hadad, Niran and Chatterjee, Emeli and Jimenez-Ramos, Maria and Farber-Eger, Eric and Roshani, Rashedeh and Stolze, Lindsey K. and Betti, Michael J. and Zhao, Shilin and Huang, Shi and Martens, Liesbet and Kendall, Timothy J. and Thoné, Tinne and Amancherla, Kaushik and Bailin, Samuel and Gabriel, Curtis L. and Koethe, John and Carr, J. Jeffrey and Terry, James Greg and Vaitinadin, Nataraja Sarma and Freedman, Jane E. and Tanriverdi, Kahraman and Alsop, Eric and Van Keuren-Jensen, Kendall and Sauld, John F.K. and Mahajan, Gautam and Khan, Sadiya S. and Colangelo, Laura and Nayor, Matthew and Fisher-Hoch, Susan and McCormick, Joseph B. and North, Kari E. and Below, Jennifer E. and Wells, Quinn S. and Abel, E. Dale and Kalhan, Ravi and Scott, Charlotte and Guilliams, Martin and Gamazon, Eric R. and Fallowfield, Jonathan A. and Banovich, Nicholas E. and Das, Saumya and Shah, Ravi}},
issn = {{2666-3791}},
journal = {{CELL REPORTS MEDICINE}},
keywords = {{NONALCOHOLIC STEATOHEPATITIS,YOUNG-ADULTS,DISEASE,NASH,SUSCEPTIBILITY,HEPATOCYTES,HOMEOSTASIS,INDUCTION,BIOMARKER,HEALTH}},
language = {{eng}},
number = {{12}},
pages = {{16}},
title = {{A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver}},
url = {{http://doi.org/10.1016/j.xcrm.2024.101871}},
volume = {{5}},
year = {{2024}},
}
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