Nucleoredoxin Downregulation Reduces β-Catenin Levels and Shifts Hematopoietic Differentiation towards Myeloid Lineage In Vitro
| Autor: | Carmen Sánchez-Bernal, Angel Hernández-Hernández, Alejandro Pérez-Fernández, Guillermo López-Ruano, Jesús Sánchez-Yagüe, Rodrigo Prieto-Bermejo |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Myeloid Cellular differentiation Wnt signaling pathway General Medicine β-catenin Biology Cell biology 03 medical and health sciences Haematopoiesis 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Downregulation and upregulation 030220 oncology & carcinogenesis Catenin medicine Stem cell Signal transduction nucleoredoxin hematopoietic differentiation |
| Zdroj: | BioChem Volume 1 Issue 1 Pages 3-35 |
| ISSN: | 2673-6411 |
| DOI: | 10.3390/biochem1010003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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