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Rescue of Angiopoietin-2 inhibits lymphatic malformation endothelial cell proliferation through antagonism of VEGFR3 signaling

GSE270271 Homo sapiens (human) Single-nucleus RNA-seq 12 samples Submitted 2025/12/30 Platform GPL18573
At a glance

Single-nucleus RNA-seq · human · 12 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). 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
12 samples: 9 × Lymphatic Malformation Endothelial Cell Line vs 3 × Control Human Dermal Lymphatic Endothelial Cell LineGroups 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
Rescue of Angiopoietin-2 Inhibits Proliferation of Lymphatic Malformation Endothelial CellsFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
Summary (written by the submitters)
Cystic lymphatic malformations (LMs) are congenital anomalies characterized by the formation of dilated lymphatic channels that can infiltrate adjacent structures and cause significant morbidity. Somatic activating single nucleotide variants in PIK3CA have been identified in the majority of these lesions, yet the precise mechanisms underlying their role in LM progression remain unclear.
Read the full summary ↓
Here, we investigated the role of Angiopoietin-2 (Ang-2) downregulation downstream of hotspot PIK3CA variants in the pathogenesis of LMs and delineated a novel inhibitory mechanism for Ang-2 in the lymphatic vasculature. Transcriptomic profiling of patient-derived lymphatic malformation endothelial cells (LM-ECs) revealed Ang-2 as one of the most significantly downregulated genes. Lentiviral overexpression of Ang-2 in LM-ECs and normal human dermal lymphatic endothelial cells significantly attenuated their proliferation by inhibiting VEGFR3 signaling via the Akt pathway. Treatment of LM-ECs with the PI3K inhibitor alpelisib, but not the mTOR inhibitor sirolimus (rapamycin), rescued Ang-2 expression and downregulated VEGFR3. Alpelisib in combination with Ang-2 overexpression produced a synergistic reduction in LM-EC proliferation compared to Ang-2 overexpression or alpelisib treatment alone. Finally, Ang-2 overexpression in LM-ECs antagonized lymphangiogenesis in a murine xenograft model of LM. Together, our findings suggest that targeting the Ang-2/VEGFR3 axis may be a viable option for the suppression of pathological lymphangiogenesis.
Published in
Rescue of Angiopoietin-2 Inhibits Proliferation of Lymphatic Malformation Endothelial Cells
Sun RW, Zhang H, Mehdi SJ et al. · FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2025 · PMID 41399917 · doi:10.1096/fj.202502078R
This dataset
Open GSE270271 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 GSE270271_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 PRJNA1126108 and SRA study SRP514969. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41399917) ↗
Study design
9 × Lymphatic Malformation Endothelial Cell Line vs 3 × Control Human Dermal Lymphatic Endothelial Cell Line

Supports a between-group comparison across 12 samples.

How we read this: 2 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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