Nucleoredoxin Downregulation Reduces β-Catenin Levels and Shifts Hematopoietic Differentiation towards Myeloid Lineage In Vitro

  1. Sánchez-Bernal, Carmen
  2. Prieto-Bermejo, Rodrigo
  3. López-Ruano, Guillermo
  4. Hernández-Hernández, Ángel
  5. Pérez-Fernández, Alejandro
  6. Sánchez-Yagüe, Jesús
  1. 1 Universidad de Salamanca
    info

    Universidad de Salamanca

    Salamanca, España

    ROR https://ror.org/02f40zc51

  2. 2 Instituto de Investigación Biomédica de Salamanca
    info

    Instituto de Investigación Biomédica de Salamanca

    Salamanca, España

    ROR https://ror.org/03em6xj44

Revista:
BioChem

ISSN: 2673-6411

Any de publicació: 2021

Volum: 1

Número: 1

Pàgines: 26-35

Tipus: Article

DOI: 10.3390/BIOCHEM1010003 GOOGLE SCHOLAR lock_openAccés obert editor

Altres publicacions en: BioChem

Objectius de Desenvolupament Sostenible

Resum

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/β-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/β-catenin pathway. Interestingly, a reduction in β-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/β-catenin pathway.

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