GEO series

Targeted p63 isoform modulation corrects dominant mutations in AEC syndrome without disrupting epidermal homeostasis [human RNA-seq]

GSE297767 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/01/07 Platform GPL24676

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: 3 × NHEK_CT vs 3 × NHEK_p63alphaKO vs 3 × HK_I537T_CT vs 3 × HK_I537T_p63alphaKOGroups 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: Therapeutic p63 isoform switching rescues epidermal defects in AEC syndromeMolecular therapy : the journal of the American Society of Gene Therapy · 2026

Summary (written by the submitters)

The transcription factor p63 is a master regulator of stratified epithelial development. Its disruption leads to severe congenital defects affecting the skin, limbs, and craniofacial structures. Among p63-related disorders, Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is caused by dominant mutations predominantly in the SAM/TID domains of the TP63 gene, affecting the p63α isoform.

Read the full summary ↓

These mutations promote protein aggregation and transcriptional dysregulation, resulting in debilitating skin erosions. To explore a therapeutic strategy based on isoform switching, we developed a conditional mouse model in which exon 13 was deleted, replacing p63α with the shorter p63β isoform, which is expressed in the skin, albeit at lower levels . Despite the essential role of p63α in limb and palate formation, we found that p63β is sufficient to sustain epidermal development, postnatal skin homeostasis, and wound healing. At the molecular level, the switch from p63α to p63β preserved chromatin binding and global transcriptional programs in keratinocytes. We next applied CRISPR/Cas9-mediated exon 13 deletion in human primary keratinocytes. This isoform conversion maintained proliferation and gene expression. Importantly, in AEC patient-derived keratinocytes, p63β expression rescued protein aggregation, restored mechanical integrity, and normalized key epidermal gene expression. Together, these findings demonstrate that p63β can functionally compensate for p63α in the skin and establish isoform switch as a promising therapeutic strategy for AEC syndrome.

Published in

Therapeutic p63 isoform switching rescues epidermal defects in AEC syndrome

Di Girolamo D, Urciuoli G, Sol S et al. · Molecular therapy : the journal of the American Society of Gene Therapy 2026 · PMID 41445194 · doi:10.1016/j.ymthe.2025.12.045

This dataset

Open GSE297767 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 GSE297767_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 PRJNA1266143 and SRA study SRP586827. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41445194) ↗

Study design

3 × NHEK_CT vs 3 × NHEK_p63alphaKO vs 3 × HK_I537T_CT vs 3 × HK_I537T_p63alphaKO

Supports a between-group comparison across 12 samples.

How we read this: 4 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

GSM8999101 NHEK_CTR1 NHEK_CT
GSM8999102 NHEK_CTR2 NHEK_CT
GSM8999103 NHEK_CTR3 NHEK_CT
GSM8999104 NHEK_p63alphaKO1 NHEK_p63alphaKO
GSM8999105 NHEK_p63alphaKO2 NHEK_p63alphaKO
GSM8999106 NHEK_p63alphaKO3 NHEK_p63alphaKO
GSM8999107 HK_I537T_CTR1 HK_I537T_CT
GSM8999108 HK_I537T_CTR2 HK_I537T_CT
GSM8999109 HK_I537T_CTR3 HK_I537T_CT
GSM8999110 HK_I537T_p63alphaKO1 HK_I537T_p63alphaKO
GSM8999111 HK_I537T_p63alphaKO2 HK_I537T_p63alphaKO
GSM8999112 HK_I537T_p63alphaKO3 HK_I537T_p63alphaKO

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