The presence of rare transient cells within pluripotent stem cell population that resemble functional and transcriptional features of totipotent 2-cell-stage embryos has emerged several questions regarding their mechanism of reactivation. Although few recent works have aimed to characterize them both at transcriptional and functional level, the mechanism of transition to 2C-like state is poorly investigated. Here we identified a new pathway, whose activation through several compounds could induce transition to 2C-like state. Interestingly, inhibition of this pathway by specific inhibitors could collectively restrain the majority of the 2C-like state transcriptional alterations including MuERV-L and Zscan4 gene family. Finally, we found that developmental potential of induced 2C-like cells could be extended to embryonic plus extra-embryonic tissues in contrast to embryonic stem cells in culture. Our finding provides a better understanding of cellular plasticity at early embryonic state, which could be important for the potential therapeutic avenues.

IDENTIFYING THE MOLECULAR PLAYERS ASSOCIATED WITH TRANSITION BETWEEN PLURIPOTENT AND TOTIPOTENT-LIKE STATES / S. Samadi Shams ; added supervisors: S. Casola,T. Stracker ; supervisor: V. Costanzo. - : . UNIVERSITA' DEGLI STUDI DI MILANO, 2017 Mar 02. ((28. ciclo, Anno Accademico 2016. [10.13130/s-samadi-shams_phd2017-03-02].

IDENTIFYING THE MOLECULAR PLAYERS ASSOCIATED WITH TRANSITION BETWEEN PLURIPOTENT AND TOTIPOTENT-LIKE STATES

S. SAMADI SHAMS
2017

Abstract

The presence of rare transient cells within pluripotent stem cell population that resemble functional and transcriptional features of totipotent 2-cell-stage embryos has emerged several questions regarding their mechanism of reactivation. Although few recent works have aimed to characterize them both at transcriptional and functional level, the mechanism of transition to 2C-like state is poorly investigated. Here we identified a new pathway, whose activation through several compounds could induce transition to 2C-like state. Interestingly, inhibition of this pathway by specific inhibitors could collectively restrain the majority of the 2C-like state transcriptional alterations including MuERV-L and Zscan4 gene family. Finally, we found that developmental potential of induced 2C-like cells could be extended to embryonic plus extra-embryonic tissues in contrast to embryonic stem cells in culture. Our finding provides a better understanding of cellular plasticity at early embryonic state, which could be important for the potential therapeutic avenues.
COSTANZO, VINCENZO
DEJANA, ELISABETTA
Cellular reprogramming ; Totipotency ; Trophoectoderm differentiation ; DNA damage response ; Embryonic development
Settore BIO/11 - Biologia Molecolare
IDENTIFYING THE MOLECULAR PLAYERS ASSOCIATED WITH TRANSITION BETWEEN PLURIPOTENT AND TOTIPOTENT-LIKE STATES / S. Samadi Shams ; added supervisors: S. Casola,T. Stracker ; supervisor: V. Costanzo. - : . UNIVERSITA' DEGLI STUDI DI MILANO, 2017 Mar 02. ((28. ciclo, Anno Accademico 2016. [10.13130/s-samadi-shams_phd2017-03-02].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/471389
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