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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-13032018-103812
Document
Author
Full name
Jenny Andrea Arévalo Romero
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Lopes, Marilene Hohmuth (President)
Coltri, Patricia Pereira
Landemberger, Michele Christine
Lee, Kil Sun
Yan, Chao Yun Irene
Title in Portuguese
Impacto da depleção da co-chaperonina STIP1 no controle da pluripotência, proliferação e diferenciação de células-tronco embrionárias murinas.
Keywords in Portuguese
Células-tronco embrionárias murinas
Co-chaperoninas
Desenvolvimento embrionário
Pluripotência
STIP1
Abstract in Portuguese
Stress Inducible Protein 1 (STIP1) é uma co-chaperonina crucial no desenvolvimento murino. Nesse contexto, estudamos as funções reguladas por STIP1 usando células-tronco embrionárias murinas (CTEm). Nosso estudo mostrou um papel regulador para STIP1 na via JAK/STAT3, incluindo os fatores de transcrição NANOG, OCT4 e SOX2, caracterizando STIP1 como agente regulador na auto-renovação e pluripotência em CTEm. Adicionalmente, STIP1 modula a diferenciação em CTEm, uma vez sua expressão é requerida na formação de corpos embrioides (EBs) normais. Adicionalmente, ensaios de formação de teratoma mostraram inibição na formação do tumor e defeitos na diferenciação já que a formação de tecidos do mesoderma foi favorecida. Além disso, foi revelada a importância de STIP1 na proliferação celular já que sua ausência afetou a função, a qual foi parcialmente resgatada com tratamento de STIP1 exógena. Desse modo, nosso trabalho revela um papel crucial para STIP1 nas CTEm, caracterizando novas funções na compreensão do papel da co-chaperonina no desenvolvimento inicial em mamíferos.
Title in English
Impact of STIP1 cochaperone depletion on the control of pluripotency, proliferation and differentiation of murine embryonic stem cells.
Keywords in English
Co-chaperones
Embryonic development
Murine embryonic stem cells
Pluripotency
STIP1
Abstract in English
Stress Inducible Phosphoprotein 1 (STIP1) is a crucial co-chaperonin in mice development. In this context, we studied the functions regulated by STIP1 using murine embryonic stem cells (CTEm). Our study shows a regulatory role for STIP1 in JAK/STAT3 pathway, including the transcription factors NANOG, OCT4 and SOX2, characterizing STIP1 as a regulatory agent in self-renewal and pluripotency in CTEm. In addition, an essential role of STIP1 in differentiation was demonstrated since its expression is required in embryoid bodies (EBs) formation with appropriate size and morphology. Moreover, teratoma formation assays showed inhibited tumor formation and defects in differentiation when formation of mesoderm was favored. Furthermore, were revealed the importance of STIP1 in cell proliferation, since its absence affects the function which was partially rescued after treatment with exogenous STIP1. Thus, our work reveals a central role for STIP1 in CTEm, characterizing new functions to understand the biological role of the co-chaperonin in early mammalian development.
 
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Publishing Date
2018-03-13
 
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