Université de Paris, URP2496, Laboratoire Pathologies, imagerie et biothérapies oro-faciales, Montrouge, France.
INSERM, UMRS_938 Centre de Recherche Saint Antoine, Paris, France.
Int J Oral Sci. 2022 Apr 2;14(1):19. doi: 10.1038/s41368-022-00169-1.
Parental imprinting is an epigenetic process leading to monoallelic expression of certain genes depending on their parental origin. Imprinting diseases are characterized by growth and metabolic issues starting from birth to adulthood. They are mainly due to methylation defects in imprinting control region that drive the abnormal expression of imprinted genes. We currently lack relevant animal or cellular models to unravel the pathophysiology of growth failure in these diseases. We aimed to characterize the methylation of imprinting regions in dental pulp stem cells and during their differentiation in osteogenic cells (involved in growth regulation) to assess the interest of this cells in modeling imprinting diseases. We collected dental pulp stem cells from five controls and four patients (three with Silver-Russell syndrome and one with Beckwith-Wiedemann syndrome). Methylation analysis of imprinting control regions involved in these syndromes showed a normal profile in controls and the imprinting defect in patients. These results were maintained in dental pulp stem cells cultured under osteogenic conditions. Furthermore, we confirmed the same pattern in six other loci involved in imprinting diseases in humans. We also confirmed monoallelic expression of H19 (an imprinted gene) in controls and its biallelic expression in one patient. Extensive imprinting control regions methylation analysis shows the strong potential of dental pulp stem cells in modeling imprinting diseases, in which imprinting regions are preserved in culture and during osteogenic differentiation. This will allow to perform in vitro functional and therapeutic tests in cells derived from dental pulp stem cells and generate other cell-types.
印记是一种表观遗传过程，导致某些基因根据其亲本来源单等位基因表达。印记疾病的特征是从出生到成年的生长和代谢问题。它们主要是由于印记控制区域的甲基化缺陷导致印记基因的异常表达。我们目前缺乏相关的动物或细胞模型来阐明这些疾病中生长衰竭的病理生理学。我们旨在描述牙髓干细胞中印记区域的甲基化及其在成骨细胞（参与生长调节）分化过程中的甲基化，以评估这些细胞在模拟印记疾病中的意义。我们从五名对照和四名患者（三名患有 Silver-Russell 综合征和一名患有 Beckwith-Wiedemann 综合征）中收集牙髓干细胞。对涉及这些综合征的印记控制区域的甲基化分析显示，对照者中存在正常的特征，而患者中存在印记缺陷。在成骨条件下培养的牙髓干细胞中，这些结果得到了维持。此外，我们在涉及人类印记疾病的六个其他基因座中证实了相同的模式。我们还在六名对照者中证实了 H19（一个印记基因）的单等位基因表达，而在一名患者中证实了其双等位基因表达。广泛的印记控制区域甲基化分析表明，牙髓干细胞在模拟印记疾病方面具有很大的潜力，在培养和成骨分化过程中，印记区域得以保留。这将允许在源自牙髓干细胞的细胞中进行体外功能和治疗测试，并生成其他细胞类型。
