engleski

Pluripotency transition in the mammalian embryo and cell cycle regulator Rb1 expression dynamics

Rb1, the retinoblastoma susceptibility gene is an important regulator of cell proliferation, apoptosis and differentiation. The pRB protein shows an important function in the cell cycle by controlling the G1/S phase transition. In its hypophosphorylated form, pRb is active and supresses the cell cycle progression, as it inactivates transcription factors (TFs), mostly from the E2F family. In G1, the formation of cyclinD/CDK4/6 complexes leads to the hyperphosphorylation of pRb loses the ability to bind E2F family of TFs, which then leads to the progression to the S phase. Methylation patterns for the retinoblastoma gene (RB1) in single human blastocysts showed 40%-60% methylation, indicating that a methylation imprint was present. Hypermethylation also occurs in most tumors, associated with the Rb1 gene disfunctions. By using molecular methods (ddPCR, pyrosequencing) and immunohistochemistry we will try to determine RB expression changes and gene regulation in pluripotency transition in rat and archive human fetal samples (GW 6-8). Expression differences between pRB and RB were found between GW 6, 7 and 8. pRB1 is expressed in differentiated, more mature cells (multi-layered epidermis, cartilage with lacunae) and absent from cells that still proliferate (pre-cartilage). Embryogenesis provides a system to investigate the roles of Rb family proteins at the interface between proliferation and differentiation.

RB1 ; embryo ; human ; plurypotency ; rat

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