Defining the transcriptome of PIK3CA-altered cells in a human capillary malformation using single cell long-read sequencing.
Humans
Class I Phosphatidylinositol 3-Kinases
/ genetics
Single-Cell Analysis
/ methods
Transcriptome
Vascular Malformations
/ genetics
Capillaries
/ pathology
Megalencephaly
/ genetics
PAX3 Transcription Factor
/ genetics
Fibroblasts
/ metabolism
Port-Wine Stain
/ genetics
High-Throughput Nucleotide Sequencing
/ methods
Mutation
Female
Male
Abnormalities, Multiple
Telangiectasis
/ congenital
Skin Diseases, Vascular
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
07
03
2024
accepted:
04
09
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic mosaic variants that result in constitutive activation of the phosphatidylinositol-3-kinase/AKT/mTOR pathway. Promising responses to molecularly targeted therapy have been reported, although identification of an appropriate agent can be hampered by the mosaic nature and corresponding low variant allele frequency of the causal variant. Moreover, our understanding of the molecular consequences of these variants-for example how they affect gene expression profiles-remains limited. Here we describe in vitro expansion of a human capillary malformation followed by molecular characterization using exome sequencing, single cell gene expression, and targeted long-read single cell RNA-sequencing in a patient with clinical features consistent with Megalencephaly-Capillary Malformation Syndrome (MCAP, a PROS condition). These approaches identified a targetable PIK3CA variant with expression restricted to PAX3+ fibroblast and undifferentiated keratinocyte populations. This study highlights the innovative combination of next-generation single cell sequencing methods to better understand unique transcriptomic profiles and cell types associated with MCAP, revealing molecular intricacies of this genetic syndrome.
Identifiants
pubmed: 39455600
doi: 10.1038/s41598-024-72167-8
pii: 10.1038/s41598-024-72167-8
doi:
Substances chimiques
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
PAX3 Transcription Factor
0
PAX3 protein, human
0
Types de publication
Journal Article
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
25440Informations de copyright
© 2024. The Author(s).
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