Generation of Primordial Germ Cell-like Cells from iPSCs Derived from Turner Syndrome Patients

Abstract

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.

Emerging Contributions of Pluripotent Stem Cells to Reproductive Technologies in Veterinary Medicine

“…The generation of iPSCs from embryonic fibroblasts or non-invasive sources (e.g., urine) from livestock species has been reported [ 101 , 102 , 103 , 104 , 105 , 106 ], and some of these studies described differentiation into germ-like cells or neuronal-like cells. In 2015, bovine-induced pluripotent stem cells (biPSCs) were induced into bovine PGCLCs (bPGCLCs) through body formation embryoids in the presence of RA and BMP4; however, the production of bPGCLCs was not shown to be efficient since only DDX4 was detected [ 107 ].…”

Current progress on in vitro differentiation of ovarian follicles from pluripotent stem cells

“…Successful derivation of PGCs and subsequent oogenesis solely from PSCs has provided insights into in-vitro gonadal formation. The understanding paves the way to solve infertility caused by congenital diseases such as turner syndrome ( Muntaj et al, 2015 ; de Souza et al, 2021 ). It is feasible to produce PGCs from patient derived iPSCs ( Yango et al, 2013 ; de Souza et al, 2021 ).…”

“…The understanding paves the way to solve infertility caused by congenital diseases such as turner syndrome ( Muntaj et al, 2015 ; de Souza et al, 2021 ). It is feasible to produce PGCs from patient derived iPSCs ( Yango et al, 2013 ; de Souza et al, 2021 ). Moreover, the establishment of disease models offers a chance to understand the mechanism of infertility, and to provide a platform for drug screening and potential therapeutic approaches.…”

Editorial for Special Issue: iPS Cells (iPSCs) for Modelling and Treatment of Human Diseases

“…In this Special Issue, we have collected articles that emphasise the wide application possibilities of iPSCs. The publications cover diseases of brain [ 2 , 3 , 4 , 5 ], kidney [ 6 ], blood [ 7 , 8 ], cartilage [ 9 ] and primordial germ cells [ 10 ] in 2D and 3D models.…”

“…The molecular basis for the associated premature primary gonadal failure in these patients is especially poorly understood. De Souza et al generated iPSCs from Turner Syndrome patients, which are suitable for modelling early germline development and resemble primary primordial germ cells regarding transcripts, protein marks and the epigenetic profile [ 10 ].…”