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Epigenetic regulation in human mesenchymal stem cells


In the last few years, studies on the use of mesenchymal stem cells (MSCs) have brought promising results on regenerative therapy, although limited. Some boundaries relies on the fact that we have little knowledge about the basic biology of these cells, especially regarding epigenetic control landscape in the dedifferentiation and multipotentiality cellular state. Amongst several epigenetic control mechanisms, the global DNA methylation and demethylation or focused on genes involved in maintaining the undifferentiated and multipotentiality cell state, are extremely relevant in this context. Understanding this scenario may contribute to the improvement of biological knowledge in what is known as health and human development and still be used in the process of cell and tissue regenerations. Aiming the better understanding of this dynamic, undifferentiated humans MSCs, derived from bone marrow and periodontal ligament and two different types of medium (with or without fetal bovine serum) will be used. The association between some enzymes involved in DNA methylation and demethylation, as DNMT1/3a/3b e TETs respectively, and some genes that encode transcription factors involved in maintaining the undifferentiated and multipotentiality cell state, such as OCT4 and NANOG, will be part of an in vitro study. For such purpose, the small molecule RG108, a DNMT1 inhibitor, will be used. Different approaches and techniques which provides DNA methylation status, either global or gene specific, gene and protein expression, enzyme activity, and multipotentiality, dedifferentiation, proliferation, viability and cell death analysis will be able to fulfill the purpose of the research. (AU)

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Scientific publications (5)
(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)
LAMEIRA, JR., ALADIM GOMES; FRANCOSO, BEATRIZ GANHITO; ABSY, SAMIR; PECORARI, VANESSA GALEGO; CASATI, MARCIO ZAFALON; RIBEIRO, FERNANDA VIEIRA; ANDIA, DENISE CARLETO. Resveratrol Reverts Epigenetic and Transcription Changes Caused by Smoke Inhalation on Bone-Related Genes in Rats. DNA AND CELL BIOLOGY, v. 37, n. 8, p. 670-679, . (14/09480-8, 13/09650-8)
FERREIRA, ROGERIO S.; ASSIS, RAHYZA I. F.; FELTRAN, GEORGIA DA S.; DO ROSARIO PALMA, IASMIN CAROLINE; FRANCOSO, BEATRIZ G.; ZAMBUZZI, WILLIAN F.; ANDIA, DENISE C.; DA SILVA, RODRIGO A.. Genome-wide DNA (hydroxy) methylation reveals the individual epigenetic landscape importance on osteogenic phenotype acquisition in periodontal ligament cells. Journal of Periodontology, . (13/09650-8, 17/12158-9)
ASSIS, RAHYZA I. F.; SCHMIDT, ARTHUR G.; RACCA, FRANCESCA; DA SILVA, RODRIGO A.; ZAMBUZZI, WILLIAM F.; SILVERIO, KARINA G.; NOCITI, FRANCISCO H.; PECORARI, VANESSA G.; WIENCH, MALGORZATA; ANDIA, DENISE C.. DNMT1 Inhibitor Restores RUNX2 Expression and Mineralization in Periodontal Ligament Cells. DNA AND CELL BIOLOGY, v. 40, n. 5, . (13/09650-8, 15/02160-0, 17/07944-5)
ADOLPHO, LETICIA FAUSTINO; LOPES, HELENA BACHA; FREITAS, GILEADE PEREIRA; WEFFORT, DENISE; CAMPOS TOTOLI, GABRIELA GUARALDO; LOYOLA BARBOSA, ANA CAROLINA; FREIRE ASSIS, RAHYZA INACIO; SILVERIO RUIZ, KARINA GONZALES; ANDIA, DENISE CARLETO; ROSA, ADALBERTO LUIZ; et al. Human periodontal ligament stem cells with distinct osteogenic potential induce bone formation in rat calvaria defects. REGENERATIVE MEDICINE, v. 17, n. 6, p. 13-pg., . (19/10076-0, 17/12622-7, 13/09650-8)
ASSIS, RAHYZA I. F.; WIENCH, MALGORZATA; SILVERIO, KARINA G.; DA SILVA, RODRIGO A.; FELTRAN, GEORGIA DA SILVA; SALLUM, ENILSON A.; CASATI, MARCIO Z.; NOCITI, JR., FRANCISCO H.; ANDIA, DENISE C.. RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation. PLoS One, v. 13, n. 12, . (13/09650-8, 15/02160-0)

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