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X-chromosome status during blood cells reprogramming in human induced pluripotent cells (iPSCs) and generation of in vitro primordial germ cells (iPGCs).

Grant number: 17/12140-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): April 01, 2018
Effective date (End): April 01, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Flávio Vieira Meirelles
Grantee:Aline Fernanda de Souza
Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
Associated research grant:13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID
Associated scholarship(s):19/08346-0 - X-chromosome remodeling in induced pluripotent cells (iPSCs) of Turner syndrome, BE.EP.PD


The embryonic development period is marked by important epigenetic processes including mechanisms of sex determination and X chromosome reprogramming. X-chromosome inactivation (XCI) is an important epigenetic marker for proper embryonic and fetal development, whereas X-chromosome reactivation (XCR) influences the pluripotent state of the cells, and thus, it is an important epigenetic modification that occurs during the generation of the primordial germ cells (PGCs). Aneuploid syndromes are caused by increased or decreased numbers of chromosomes and represent an extreme example of development diseases, one important example is the Turner's syndrome, which affects women and leads to infertility. The in vitro modeling of these syndromes is relevant to clinical and basic research aspects once it may provide advanced knowledge on the etiology and new therapies possibilities to its condition. This proposal aim to evaluate the XCI and XCR during the induction into pluripotency of cell lineages (iPSCs) from Turner's syndrome carrier's patients, as well as from patients that do not carry any X chromosome related syndrome, and its posterior inducing to human primordial germ cells in vitro (iPGCs) to evaluate the X chromosome remodeling. For such, the following techniques will be emplpoyed: cellular reprogramming to pluripotent from blood cells and induction into iPGCs; cellular characterization of these through detection of pluripotent and germinative markers; and evaluation of XCI and XCR stages according to the of HUMARA assay and XIST genes. This proposal will elucidate fundamental concepts of X chromosome remodeling, resulting in an important advance to the genetic and epigenetic knowledge of human reproductive medicine.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE SOUZA, ALINE FERNANDA; BRESSAN, FABIANA FERNANDES; PIERI, NAIRA CAROLINE GODOY; BOTIGELLI, RAMON CESAR; REVAY, TAMAS; HADDAD, SIMONE KASHIMA; COVAS, DIMAS TADEU; RAMOS, ESTER SILVEIRA; KING, WILLIAN ALLAN; MEIRELLES, FLAVIO VIEIRA. Generation of Primordial Germ Cell-like Cells from iPSCs Derived from Turner Syndrome Patients. CELLS, v. 10, n. 11, . (19/08346-0, 14/50947-7, 17/12140-2, 13/08135-2, 15/26818-5)

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