GEO series

Integrative gene regulatory analysis reveals transcriptional mechanisms required in mature human hepatocytes and during in vitro hepatocyte differentiation (scRNA-Seq)

GSE182604 Homo sapiens (human) Single-cell RNA-seq 18 samples Submitted 2024/08/22 Platform GPL18573

At a glance

Single-cell RNA-seq · human · 18 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Homo sapiens (human)
Samples: 18 samples: 9 × PHH vs 2 × ICO3-DM vs 2 × ICO3-EMGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Multi-omics analysis reveals distinct gene regulatory mechanisms between primary and organoid-derived human hepatocytesDisease models & mechanisms · 2025

Summary (written by the submitters)

Advances in 3D cell culture systems, including the hepatic organoids, has shown the potential to model the liver development in vitro. However, hepatocyte-like cells obtained by these means are still immature compared to the primary human hepatocytes. Here we applied single-cell RNA-seq and ATAC-seq to identify gene regulatory mechanisms distinct to mature human hepatocytes (in vivo) and organoid derived hepatocyte like cells (in vitro).

Read the full summary ↓

Using a modified two-step perfusion protocol, primary hepatocytes from all lobular zones were obtained with high purity. Integrative analysis revealed a key role of transcription factors of the AP-1 family in cooperation with hepatocyte-specific transcription factors, such as HNF4A, in establishing cellular identity of mature hepatocytes. Furthermore, it revealed distinct transcription factor sets required/active in human hepatocytes and liver organoids. Function analysis of an organoid-enriched transcription factor ELF3, showed that decreased expression of ELF3 in liver organoids promotes increased expression of genes typical to mature hepatocytes. This study indicates that ELF3 functions as a barrier of hepatocyte differentiation from liver organoids. Collectively, our integrative analysis provides critical insights into the transcriptional regulatory networks of human hepatocytes and liver organoids, which will further efficient differentiation of functional hepatocytes in vitro.

Published in

Multi-omics analysis reveals distinct gene regulatory mechanisms between primary and organoid-derived human hepatocytes

Wu H, Yang ASP, Stelloo S et al. · Disease models & mechanisms 2025 · PMID 39878507 · doi:10.1242/dmm.050883

This dataset

Open GSE182604 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE182604_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA756999 and SRA study SRP333733. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39878507) ↗

Study design

9 × PHH vs 2 × ICO3-DM vs 2 × ICO3-EM

Supports a between-group comparison across 13 samples.

How we read this: 3 replicated groups read from 18 sample titles; they account for 13 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM5532192 ICO1-DM_1544
GSM5532193 ICO1-EM_1543
GSM5532194 ICO1-EMDM_1344
GSM5532195 ICO2-DM_1065
GSM5532196 ICO2-EM_1067
GSM5532197 ICO3-DM_972 ICO3-DM
GSM5532198 ICO3-DM_973 ICO3-DM
GSM5532199 ICO3-EM_974 ICO3-EM
GSM5532200 ICO3-EM_975 ICO3-EM
GSM5532201 PHH_1335 PHH
GSM5532202 PHH_1336 PHH
GSM5532203 PHH_1337 PHH
GSM5532204 PHH_1338 PHH
GSM5532205 PHH_1339 PHH
GSM5532206 PHH_1340 PHH
GSM5532207 PHH_1341 PHH
GSM5532208 PHH_1342 PHH
GSM5532209 PHH_1343 PHH

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