Nucleoredoxin downregulation reduces β-Catenin levels and shifts hematopoietic differentiation towards myeloid lineage in vitro

[EN]The importance of dissecting signaling pathways governing cell differentiation is based on their relevance not only for understanding basic biological phenomena but also for better comprehending the underlying mechanisms of pathologic alterations such as cancer. A paradigm of cell differentiatio...

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Detalles Bibliográficos
Autores: Pérez Fernández, Alejandro, López Ruano, Guillermo, Prieto Bermejo, Rodrigo, Sánchez Bernal, María Carmen, Sánchez Yagüe, Jesús, Hernández Hernández, Ángel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/155154
Acceso en línea:http://hdl.handle.net/10366/155154
Access Level:acceso abierto
Palabra clave:Nucleoredoxin
β-catenin
Hematopoietic differentiation
Hematopoiesis
hematopoyesis
Descripción
Sumario:[EN]The importance of dissecting signaling pathways governing cell differentiation is based on their relevance not only for understanding basic biological phenomena but also for better comprehending the underlying mechanisms of pathologic alterations such as cancer. A paradigm of cell differentiation processes is hematopoiesis, where a single stem cell gives rise to multiple, fully differentiated, cell lineages. Nucleoredoxin (Nrx), a member of the thioredoxin family, is an important redox-sensitive modulator of Wnt/ -catenin signaling, a key pathway for the control of hematopoiesis. In this work, the relevance of Nrx for the differentiation of mouse hematopoietic progenitor cells has been analyzed in vitro. Nrx silencing leads to a dramatic reduction in the size of the Lin and LSK progenitor populations. Moreover, there is also a remarkable decrease in CD3+ cells and an enhancement in the percentage of CD11b+Gr1 myeloid cells. This myeloid bias would agree with the inhibition of the Wnt/ -catenin pathway. Interestingly, a reduction in -catenin at the protein level was observed upon Nrx silencing. Our results strongly support the importance of Nrx for hematopoietic differentiation, which could be mediated by the regulation of the Wnt/ -catenin pathway.