Generation of Primordial Germ Cell-like Cells from iPSCs Derived from Turner Syndrome Patients
Aline Fernanda de Souza,
Fabiana Fernandes Bressan,
Naira Caroline Godoy Pieri,
Ramon Cesar Botigelli,
Tamas Revay,
Simone Kashima Haddad,
Dimas Tadeu Covas,
Ester Silveira Ramos,
Willian Allan King,
Flavio Vieira Meirelles
Affiliations
Aline Fernanda de Souza
Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo (USP), Pirassununga 13635-000, Brazil
Fabiana Fernandes Bressan
Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo (USP), Pirassununga 13635-000, Brazil
Naira Caroline Godoy Pieri
Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo (USP), Pirassununga 13635-000, Brazil
Ramon Cesar Botigelli
Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo (USP), Pirassununga 13635-000, Brazil
Tamas Revay
Department Alberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB T2N 4N1, Canada
Simone Kashima Haddad
Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14051-060, Brazil
Dimas Tadeu Covas
Center for Cell-Based Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14051-060, Brazil
Ester Silveira Ramos
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil
Willian Allan King
Department of Biomedical Sciences, Ontario Veterinary College (OVC), University of Guelph, Guelph, ON N1G 2W1, Canada
Flavio Vieira Meirelles
Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo (USP), Pirassununga 13635-000, Brazil
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.
