High importance
Sep 7, 2026
To generate and characterize two induced pluripotent stem cell (iPSC) lines from hereditary hemorrhagic telangiectasia (HHT) patients with specific ACVRL1 mutations.
Patient-derived iPSC lines were created from clinically diagnosed HHT donors with heterozygous ACVRL1 mutations. These lines were assessed for iPSC morphology, expression of undifferentiated markers, genomic stability through low-pass whole genome sequencing (LP-WGS), and their capacity for tri-lineage differentiation.
The generated iPSC lines exhibited expected morphology, robust expression of undifferentiated markers, maintained genomic stability, and demonstrated the ability to differentiate into three germ layers, confirming their pluripotency.
The study focused on only two specific ACVRL1 mutations and may not encompass the full range of genetic diversity in the HHT patient population. Further functional studies are needed to assess the implications of haploinsufficiency in vascular development.
These iPSC lines provide vital resources for investigating the molecular mechanisms of HHT and the role of ACVRL1 in vascular pathobiology, potentially guiding therapeutic developments for patients suffering from this condition.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder in which dysregulated endothelial signaling drives telangiectasias and arteriovenous malformations across multiple organs. Loss-of-function variants in ACVRL1 (ALK1), a core receptor in BMP9/10 signaling, are a major genetic cause. Here we report two patient-derived induced pluripotent stem cell (iPSC) lines generated from clinically diagnosed HHT donors carrying heterozygous ACVRL1 mutations: c.129dup (p.Pro44Alafs*125) and c.430C > T (p.Arg144*). Both lines showed expected iPSC morphology, robust expression of markers of the undifferentiated iPSC state, genomic stability by LP-WGS, and tri-lineage differentiation capacity. These resources enable human cell-based studies of ACVRL1 haploinsufficiency and provide a starting point for mechanistic and therapeutic work focused on HHT vascular pathobiology.