Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo (USP), Pirassununga 13635-000, Brazil.
Department of Biomedical Sciences, Ontario Veterinary College (OVC), University of Guelph, Guelph, ON N1G 2W1, Canada.
Cells. 2021 Nov 10;10(11):3099. doi: 10.3390/cells10113099.
Turner syndrome (TS) is a genetic disorder in females with X Chromosome monosomy associated with highly variable clinical features, including premature primary gonadal failure leading to ovarian dysfunction and infertility. The mechanism of development of primordial germ cells (PGCs) and their connection with ovarian failure in TS is poorly understood. An in vitro model of PGCs from TS would be beneficial for investigating genetic and epigenetic factors that influence germ cell specification. Here we investigated the potential of reprogramming peripheral mononuclear blood cells from TS women (PBMCs-TS) into iPSCs following in vitro differentiation in hPGCLCs. All hiPSCs-TS lines demonstrated pluripotency state and were capable of differentiation into three embryonic layers (ectoderm, endoderm, and mesoderm). The PGCLCs-TS recapitulated the initial germline development period regarding transcripts and protein marks, including the epigenetic profile. Overall, our results highlighted the feasibility of producing in vitro models to help the understanding of the mechanisms associated with germ cell formation in TS.
特纳综合征(Turner syndrome,TS)是一种女性遗传性疾病,伴 X 染色体单体性,具有高度可变的临床特征,包括导致卵巢功能障碍和不孕的原发性性腺功能衰竭。原始生殖细胞(primordial germ cells,PGCs)的发育机制及其与 TS 中卵巢衰竭的关系尚不清楚。来自 TS 的 PGCs 的体外模型将有利于研究影响生殖细胞特化的遗传和表观遗传因素。在这里,我们研究了在 hPGCLCs 中体外分化后将 TS 女性的外周血单核细胞(peripheral mononuclear blood cells from TS women,PBMCs-TS)重编程为 iPSCs 的潜力。所有 hiPSCs-TS 系均表现出多能性状态,并能够分化为三个胚胎层(外胚层、内胚层和中胚层)。PGCLCs-TS 重现了关于转录物和蛋白质标记的初始生殖细胞发育时期,包括表观遗传特征。总体而言,我们的结果强调了产生体外模型的可行性,以帮助理解与 TS 中生殖细胞形成相关的机制。