ESPE Abstracts (2022) 95 RFC7.5


1Sorbonne Université, Paris, France; 2AP-HP, Paris, France; 3Université Paris Cité, Paris, France; 4AP-HP, Kremlin-Bicêtre, France; 5Université Paris-Saclay, Kremlin-Bicêtre, France

Parental imprinting is an epigenetic process leading to monoallelic expression of certain genes depending on their parental origin. Imprinting disorders are a set of rare diseases that mainly affect growth and metabolism from birth to adulthood. These disorders are mainly due to methylation defects in imprinting control region that drive the abnormal expression of imprinted genes. Moreover, patients with imprinting disorders may present overlapping clinical features that can be explained by the co-regulation of imprinted genes that belong to a dynamic imprinted gene network. We currently lack relevant animal or cellular models to understand the pathophysiology of growth failure in imprinting disorders. Multipotent stem cells could be a promising alternative. In this context, we aimed to assess the relevance of mesenchymal stem cells derived from the dental pulp and osteogenic cells derived to their differentiation in modelling imprinting disorders. We collected dental pulp stem cells from five controls and seven patients (five with Silver-Russell syndrome, one with Temple syndrome and one with Beckwith-Wiedemann syndrome) and we cultured them under osteogenic conditions. We reported that methylation of imprinting control regions involved in these syndromes showed a normal profile in controls and the imprinting defect in patients. Besides, in three patients with Silver-Russell syndrome and one patient with Beckwith-Wiedemann syndrome we showed that these results were maintained in dental pulp stem cells derivation in osteogenic cells. An extensive analysis of methylation allowed us to confirmed the same pattern in six other loci involved in imprinting disorders in humans. Aside from methylation profile, we also confirmed monoallelic expression of H19 (an imprinted gene at the 11p15.5 region) in controls and its biallelic expression in one patient using a newly developed method based on SNP-genotyping RTQPCR. These data were concordant with the methylation profiles in both controls and patients and validate the imprint maintenance in these cells. In conclusion, this extensive imprinting control regions methylation analysis shows the potential of dental pulp stem cells in modelling imprinting diseases, in which imprinting regions are preserved in culture and during osteogenic differentiation. The availability of such a cellular model will allow to perform in vitro functional and therapeutic tests in cells derived from dental pulp stem cells. Further work has to be done to generate other cell-types responsible for phenotype in patients with imprinting disorders, such as chondrocytes or adipocytes.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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