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Phosphatidylserine and RhoB connect phosphatidylinositol 4-phosphate and phosphatidic acid metabolism at the plasma membrane

GSE308521 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/12/04 Platform GPL18573
At a glance

RNA-seq (gene expression) · human · 12 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
Homo sapiens (human)
Samples
12 samples: 6 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
Phosphatidylserine and RhoB connect phosphatidylinositol 4-phosphate and phosphatidic acid metabolism at the plasma membranebioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Cells tightly control the homeostatic levels and subcellular localizations of membrane phospholipids through the regulation of the activities of numerous lipid-metabolizing enzymes and lipid transfer proteins. Yet, the mechanisms by which lipid imbalances are sensed and corrected to establish and maintain homeostasis are, in many cases, unknown.
Read the full summary ↓
Here we present an expanded view of plasma membrane phosphoinositide metabolism by revealing an unexpected metabolic connection between two key anionic lipids in this membrane, phosphatidylinositol 4-phosphate (PI4P) and phosphatidic acid (PA). Plasma membrane pools of PI4P are generated by PI 4-kinase Type IIIα (PI4KIIIα/PI4KA), an essential enzyme whose partial dysfunction leads to numerous hereditary human diseases. We find that depletion of PI4P by pharmacological inhibition of PI4KA increases the activity of phospholipase Ds (PLDs) and the levels of their lipid product, PA. Guided by RNA-seq analysis and proximity labeling proteomics, we elucidate how cells connect this PI4P decrease to a compensatory increase in PA levels. Loss of plasma membrane PI4P induces a concomitant decrease of phosphatidylserine (PS) levels, and this metabolic rewiring activates a reciprocal relationship between PS synthesis and PLD-mediated PA generation. These metabolic changes lead to transcriptional and translational upregulation of the small GTPase RhoB, which enhances PLD-mediated PA synthesis and subsequent actin cytoskeletal remodeling. Our study reveals how disease-relevant perturbation of phosphoinositide synthesis induces an integrated response that ultimately boosts levels of a key anionic lipid and metabolic intermediate in phosphoinositide resynthesis.
Published in
Phosphatidylserine and RhoB connect phosphatidylinositol 4-phosphate and phosphatidic acid metabolism at the plasma membrane
Huang S, Kim YJ, Cao X et al. · bioRxiv : the preprint server for biology 2025 · PMID 41256676 · doi:10.1101/2025.09.30.679611
This dataset
Open GSE308521 in finder → Find more human 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 GSE308521_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 PRJNA1330818 and SRA study SRP621936. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41256676) ↗
Study design
6 conditions, mostly in duplicate
RPF_0min ×2 RPF_60min ×2 RPF_360min ×2 mRNA_0min ×2 mRNA_60min ×2 mRNA_360min ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 12 sample titles; they account for 12 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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