GEO series
A novel sorting method uncovers metabolic heterogeneity between mononucleated and binucleated tetraploid hepatocytes
GSE324432
Mus musculus
Expression profiling by high throughput sequencing
15 samples
Submitted 2026/08/07
Platform GPL24247
Summary
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. 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
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
Download
Direct links to NCBI, no account and no request form: the whole study as GSE324432_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 15 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1435089 and SRA study SRP682589. Searching any of these in the dataset finder brings you back here.
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.
4 replicated groups read from 15 sample titles; they account for 15 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9576095 hepatocytes, 2n-whole, subject1
- GSM9576096 hepatocytes, 2n-whole, subject2
- GSM9576097 hepatocytes, 2n-whole, subject3
- GSM9576098 hepatocytes, 2n-whole, subject4
- GSM9576099 hepatocytes, 4n-whole, subject1
- GSM9576100 hepatocytes, 4n-whole, subject2
- GSM9576101 hepatocytes, 4n-whole, subject3
- GSM9576102 hepatocytes, 4n-whole, subject4
- GSM9576103 hepatocytes, 4n-bottom, subject1
- GSM9576104 hepatocytes, 4n-bottom, subject2
- GSM9576105 hepatocytes, 4n-bottom, subject3
- GSM9576106 hepatocytes, 4n-bottom, subject4
- GSM9576107 hepatocytes, 4n-top, subject2
- GSM9576108 hepatocytes, 4n-top, subject3
- GSM9576109 hepatocytes, 4n-top, subject4
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