Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation.

ABSTRACT: In the mammalian liver, hepatocytes exhibit diverse metabolic and functional profiles based on their location within the liver lobule. However, it is unclear whether this spatial variation, called zonation, is governed by a well-defined gene regulatory code. Here, using a combination of single-cell multiomics, spatial omics, massively parallel reporter assays and deep learning, we mapped enhancer-gene regulatory networks across mouse liver cell types. We found that zonation affects gene expression and chromatin accessibility in hepatocytes, among other cell types. These states are driven by the repressors TCF7L1 and TBX3, alongside other core hepatocyte transcription factors, such as HNF4A, CEBPA, FOXA1 and ONECUT1. To examine the architecture of the enhancers driving these cell states, we

SUBMITTER: Bravo Gonzalez-Blas C 

PROVIDER: S-EPMC10791584 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature