Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Spatial Computational Hepatic Molecular Biomarker Reveals LSECs Role in Mid Lobular Liver Zonation Fibrosis in DILI and NASH Induced Liver Injury

Version 1 : Received: 3 January 2024 / Approved: 4 January 2024 / Online: 4 January 2024 (07:10:59 CET)

How to cite: Puri, M. Spatial Computational Hepatic Molecular Biomarker Reveals LSECs Role in Mid Lobular Liver Zonation Fibrosis in DILI and NASH Induced Liver Injury. Preprints 2024, 2024010361. https://doi.org/10.20944/preprints202401.0361.v1 Puri, M. Spatial Computational Hepatic Molecular Biomarker Reveals LSECs Role in Mid Lobular Liver Zonation Fibrosis in DILI and NASH Induced Liver Injury. Preprints 2024, 2024010361. https://doi.org/10.20944/preprints202401.0361.v1

Abstract

Liver is structurally organized into zonation where LSECs endothelial cells play a crucial role during chronic liver injury and early stages of fibrosis. Fibrosis can be reversed if diagnosed early at molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in normal and diseased fibrotic human liver. DEG analysis is performed over LSECs and identified the top 20 expressed genes in periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells figured out OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, CTSL genes as expressed in DILI and NASH ECs populations. The connection between LSECs marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases.

Keywords

DILI; NASH; liver zonation marker; bridging fibrosis; spatial transcriptomics; liver injury; computational biomarker; LSEC

Subject

Medicine and Pharmacology, Pathology and Pathobiology

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