GEO series

Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth [bulk RNA-seq]

GSE264260 Homo sapiens (human) Single-cell RNA-seq 38 samples Submitted 2024/04/30 Platform GPL18573

At a glance

Single-cell RNA-seq · human · 38 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Homo sapiens (human)
Samples: 38 samples: 19 conditions, mostly in duplicateGroups 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: Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growthNature communications · 2024

Summary (written by the submitters)

Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, human fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary human hepatocyte (PHH) organoids remain difficult to expand, suggesting different growth requirements between fetal and adult hepatocytes.

Read the full summary ↓

Here, we characterize hepatocyte organoid outgrowth using temporal transcriptomic and phenotypic approaches. FHs initiate reciprocal transcriptional programs involving increased proliferation and repressed lipid metabolism upon initiation of organoid growth. We exploited these insights to design maturation conditions for FH organoids, resulting in acquisition of mature hepatocyte morphological traits and increased expression of functional markers. During PHH organoid outgrowth in the same culture condition, the adult transcriptomes initially mimic the fetal transcriptomic signatures, but PHHs rapidly acquire disbalanced proliferation-lipid metabolism dynamics, resulting in steatosis and halted organoid growth. IL6 supplementation, as emerged from the fetal dataset, and simultaneous activation of the metabolic regulator FXR, prevents steatosis and promotes PHH proliferation, resulting in improved expansion of the derived organoids. Single-cell RNA sequencing analyses reveal preservation of their fetal and adult hepatocyte identities in the respective organoid cultures. Our findings uncover mitogen requirements and metabolic differences determining proliferation of hepatocytes changing from development to adulthood.

Published in

Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth

Hendriks D, Artegiani B, Margaritis T et al. · Nature communications 2024 · PMID 38740814 · doi:10.1038/s41467-024-48550-4

This dataset

Open GSE264260 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 GSE264260_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 PRJNA1101687. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38740814) ↗

Study design

19 conditions, mostly in duplicate

tissue_FHdono ×2 cells_FHdono ×2 14h_FHdono ×2 24h_FHdono ×2 48h_FHdono ×2 72h_FHdono ×2 7d_FHdono ×2 ps+1d_FHdono ×2 +11 more

Supports a between-group comparison across 38 samples.

How we read this: 19 replicated groups read from 38 sample titles; they account for 38 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

GSM8215136 tissue_FHdonor1 tissue_FHdono
GSM8215137 cells_FHdonor1 cells_FHdono
GSM8215138 14h_FHdonor1 14h_FHdono
GSM8215139 24h_FHdonor1 24h_FHdono
GSM8215140 48h_FHdonor1 48h_FHdono
GSM8215141 72h_FHdonor1 72h_FHdono
GSM8215142 7d_FHdonor1 7d_FHdono
GSM8215143 ps+1d_FHdonor1 ps+1d_FHdono
GSM8215144 tissue_FHdonor2 tissue_FHdono
GSM8215145 cells_FHdonor2 cells_FHdono
GSM8215146 14h_FHdonor2 14h_FHdono
GSM8215147 24h_FHdonor2 24h_FHdono
GSM8215148 48h_FHdonor2 48h_FHdono
GSM8215149 72h_FHdonor2 72h_FHdono
GSM8215150 7d_FHdonor2 7d_FHdono
GSM8215151 ps+1d_FHdonor2 ps+1d_FHdono
GSM8215152 sc_0h_FHdonor1 sc_0h_FHdono
GSM8215153 sc_14h_FHdonor1 sc_14h_FHdono
GSM8215154 sc_24h_FHdonor1 sc_24h_FHdono
GSM8215155 sc_48h_FHdonor1 sc_48h_FHdono
GSM8215156 sc_72h_FHdonor1 sc_72h_FHdono
GSM8215157 sc_0h_FHdonor3 sc_0h_FHdono
GSM8215158 sc_14h_FHdonor3 sc_14h_FHdono
GSM8215159 sc_24h_FHdonor3 sc_24h_FHdono
GSM8215160 sc_48h_FHdonor3 sc_48h_FHdono
GSM8215161 sc_72h_FHdonor3 sc_72h_FHdono
GSM8215162 cells_PHHdonor1 cells_PHHdono
GSM8215163 14h_PHHdonor1 14h_PHHdono
GSM8215164 24h_PHHdonor1 24h_PHHdono
GSM8215165 48h_PHHdonor1 48h_PHHdono
GSM8215166 7d_PHHdonor1 7d_PHHdono
GSM8215167 ps+1d_PHHdonor1 ps+1d_PHHdono
GSM8215168 cells_PHHdonor2 cells_PHHdono
GSM8215169 14h_PHHdonor2 14h_PHHdono
GSM8215170 24h_PHHdonor2 24h_PHHdono
GSM8215171 48h_PHHdonor2 48h_PHHdono
GSM8215172 7d_PHHdonor2 7d_PHHdono
GSM8215173 ps+1d_PHHdonor2 ps+1d_PHHdono

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