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A novel sorting method uncovers metabolic heterogeneity between mononucleated and binucleated tetraploid hepatocytes

GSE324432 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2026/08/07 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 15 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
15 samples: 4 × hepatocytes, 2n-whole, subject vs 4 × hepatocytes, 4n-whole, subject vs 4 × hepatocytes, 4n-bottom, subject vs 3 × hepatocytes, 4n-top, subjectGroups 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
A novel sorting method uncovers metabolic heterogeneity between mononucleated and binucleated tetraploid hepatocytesThe Journal of biological chemistry · 2026
Summary (written by the submitters)
Hepatocytes display notable ploidy diversity, varying both in the number of genomic copies and in the number of nuclei. In adult mice, more than 50% of hepatocytes are tetraploid (4n), which can exist as either mononucleated (1x4n) or binucleated (2x2n) cells. Despite this distinction, these two cell types have traditionally been grouped and studied as a single population.
Read the full summary ↓
One likely reason for this is that conventional ploidy-sorting methods classify hepatocytes based solely on total DNA content, without distinguishing between mononucleated and binucleated states. Consequently, it remains unclear whether 1x4n and 2x2n hepatocytes are functionally equivalent. In this study, we developed a novel FACS strategy to distinguish and isolate 1x4n and 2x2n hepatocytes. Our approach leverages Hoechst-area to assess total ploidy and Hoechst-height to differentiate mononucleated and binucleated hepatocytes. Transcriptome analysis comparing these two populations revealed that 1x4n hepatocytes exhibit a broader and more metabolically active gene expression profile. Importantly, these metabolic gene expression programs were independent of liver zonation, a well-known driver of metabolic heterogeneity in hepatocytes. Our findings uncover a previously underappreciated layer of functional diversity in the liver and provide a new framework for studying the physiological and pathological roles of nuclear configuration in hepatocytes.
Published in
A novel sorting method uncovers metabolic heterogeneity between mononucleated and binucleated tetraploid hepatocytes
Watanabe YV, Sussman JH, Anami T et al. · The Journal of biological chemistry 2026 · PMID 42442498 · doi:10.1016/j.jbc.2026.113324
This dataset
Open GSE324432 in finder → Find more mouse 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 GSE324432_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1435089 and SRA study SRP682589. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42442498) ↗
Study design
4 × hepatocytes, 2n-whole, subject vs 4 × hepatocytes, 4n-whole, subject vs 4 × hepatocytes, 4n-bottom, subject vs 3 × hepatocytes, 4n-top, subject

Supports a between-group comparison across 15 samples.

How we read this: 4 replicated groups read from 15 sample titles; they account for 15 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
Datasets on a similar topic

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