Cazaux Mateus Francisca, Camões Dos Santos João, Arez Maria, Bekman Evguenia P, da Rocha Simão T
Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.
Associate Laboratory i4HB, Institute for Health and Bioeconomy, Lisbon, Portugal.
Hum Cell. 2025 Sep 16;38(6):161. doi: 10.1007/s13577-025-01287-8.
Angelman syndrome is a rare neurodevelopmental disorder caused by the loss of function of the maternally inherited UBE3A gene within the chr15q11-q13 region. This gene is subjected to a tissue-specific form of genomic imprinting leading to the silencing of the paternal allele in neurons. Angelman syndrome can result from various (epi)genetic mechanisms, with paternal uniparental disomy of chromosome 15 (patUPD15) being one of the rarest and least studied due to the absence of suitable models. To address this gap, we generated three independent induced pluripotent stem cell (iPSC) lines from individuals with Angelman syndrome caused by patUPD15, alongside genetically matched unaffected familial controls. Peripheral blood mononuclear cells (PBMCs) were reprogrammed into iPSCs using a non-integrative Sendai virus-based approach expressing the Yamanaka factors. All iPSC lines underwent rigorous quality control, confirming stem cell identity, trilineage differentiation potential, and genetic and epigenetic integrity. This newly established iPSC toolkit provides a powerful platform to investigate the molecular underpinnings of Angelman syndrome caused by patUPD15, paving the way for future translational research and therapeutic development tailored for this understudied form of the disorder.
天使综合征是一种罕见的神经发育障碍，由15号染色体q11-q13区域内母系遗传的UBE3A基因功能丧失引起。该基因受到一种组织特异性的基因组印记形式的影响，导致父本等位基因在神经元中沉默。天使综合征可由多种（表观）遗传机制引起，由于缺乏合适的模型，父源单亲二体15（patUPD15）是最罕见且研究最少的机制之一。为了填补这一空白，我们从因patUPD15导致天使综合征的个体中生成了三个独立的诱导多能干细胞（iPSC）系，以及基因匹配的未受影响的家族对照。使用表达山中因子的基于仙台病毒的非整合方法，将外周血单个核细胞（PBMC）重编程为iPSC。所有iPSC系都经过了严格的质量控制，确认了干细胞身份、三系分化潜能以及遗传和表观遗传完整性。这个新建立的iPSC工具包为研究由patUPD15引起的天使综合征的分子基础提供了一个强大的平台，为未来针对这种研究不足的疾病形式的转化研究和治疗开发铺平了道路。
