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Molecular mechanisms involved in the transition between the primed into naive state of embryonic stem cells

Grant number: 17/15929-6
Support type:Scholarships in Brazil - Master
Effective date (Start): January 01, 2018
Effective date (End): December 31, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Rodrigo Alexandre Panepucci
Grantee:Amanda Cristina Corveloni
Home Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil

Abstract

Mouse Embryonic Stem Cells (ESC) can be derived from internal cellular mass of blastocyst in pre and post-implantation, originating, respectively, mESC or EpiSCs. In vitro, these cells present different functional, phenotypic, epigenetic and molecular characteristics. The mESC (Naïve) are considered more primitive and undifferentiated, meanwhile the EpiSCs (Primed) would be already prepared to respond to inductors signals to different germ layers. Human CTEhs have traces of Primed cells, however they can be reversed to Naïve state by using pharmacological inhibitors of certain pathways. Recently, by using a quantitative and automated fluorescent microscopy approach (High Content Analysis, HCA), our group has identified post-pluripotent microRNAs at human ESC of H1 lineage and our results indicate that inhibition of Notch pathway, by post-transcriptional mechanisms, is linked to maintenance/induction of pluripotency. Together with literature data, these results indicate that Notch pathway is associated to Primed state in ESC, however, its function in Naive/Primed transition has not been investigated. Hence, the objective of this work is, by using H1 (XY) and H9 (XX) lineage of human embryonic stem cell, establish a Naive/Primed reversion process, using Lif-3i method and characterize the phenotypic, epigenetic and transcriptional conversion, and also in H9 lineage, the inactivation of X chromosome. Then, Primed and Naïve cells will be compared on Notch pathway activation and later, the role of this pathway will be evaluated by silencing its components, by using siRNAs.

Matéria(s) publicada(s) na Agência FAPESP sobre a bolsa:
New mechanisms that regulate pluripotency in embryonic stem cells are discovered