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X-chromosome remodeling in induced pluripotent cells (iPSCs) of Turner syndrome

Grant number: 19/08346-0
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): August 15, 2019
Effective date (End): August 14, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Flávio Vieira Meirelles
Grantee:Aline Fernanda de Souza
Supervisor: William Allan King
Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
Research place: University of Guelph, Canada  
Associated to the scholarship:17/12140-2 - X-chromosome status during blood cells reprogramming in human induced pluripotent cells (iPSCs) and generation of in vitro primordial germ cells (iPGCs)., BP.PD


Induced pluripotent stem cells (iPSCs) obtained from different tissues allow us to generate relevant cell types that enable the formation or repair of damaged tissue and the generation of new in vitro models of syndromes or diseases. Moreover, human embryonic stem cells (hESCs) and iPSCs have recently been used to induced primordial germ cells like (PGCs-like), making then of great interest for cell therapy and for progressing reproductive biotechnologies. Aneuploid syndromes are caused by increased or decreased numbers of chromosomes and represent an extreme example of developmental diseases. One important example is the Turner syndrome (TS), a human genetic disorder in females who lack all or part of one X chromosome. The phenotype results in development of highly variable clinical features including ovarian dysfunction leading to infertility, altered regulation of gene expression and epigenetic changes involving differential DNA methylation. The in vitro modeling of TS presents an opportunity to investigate genetic and epigenetic factors that influence germ cell development. The objective of this proposal is to evaluate X chromosome remodeling during hiPSCs and PGCs-like from TS carriers, as well as from patients that do not carry any X chromosome related syndrome. For this, it will be applied multiple techniques, such as fluorescence in situ hybridization (FISH), RNA- FISH, staining by immunofluorescence of histone, Real-Time Polymerase Chain Reaction Analysis (RT-qPCR), and Western Blot. It is noteworthy, that this BEPE will be developed jointly with our previously formed partnership with Dr. W. Allan King, professor of the Department of Biomedical Science of the University of Guelph. Dr. King has extensive expertise on the cytogenetic and epigenetic profile. This proposal will elucidate the fundamental concepts of X-chromosome remodeling in hiPSCs. In addition, results obtained in this project will be applied to several fields of knowledge related to human basic science. (AU)

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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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