Alejandro Pérez-Fernández, Guillermo López-Ruano, Rodrigo Prieto-Bermejo, C. Sánchez-Bernal, J. Sánchez-Yagüe, Á. Hernández-Hernández
{"title":"核氧还蛋白下调可降低β-连环蛋白水平并使体外造血分化向髓系谱系转移","authors":"Alejandro Pérez-Fernández, Guillermo López-Ruano, Rodrigo Prieto-Bermejo, C. Sánchez-Bernal, J. Sánchez-Yagüe, Á. Hernández-Hernández","doi":"10.3390/BIOCHEM1010003","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":72357,"journal":{"name":"BioChem","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2021-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nucleoredoxin Downregulation Reduces β-Catenin Levels and Shifts Hematopoietic Differentiation towards Myeloid Lineage In Vitro\",\"authors\":\"Alejandro Pérez-Fernández, Guillermo López-Ruano, Rodrigo Prieto-Bermejo, C. Sánchez-Bernal, J. Sánchez-Yagüe, Á. Hernández-Hernández\",\"doi\":\"10.3390/BIOCHEM1010003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":72357,\"journal\":{\"name\":\"BioChem\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-04-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BioChem\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/BIOCHEM1010003\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BioChem","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/BIOCHEM1010003","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Nucleoredoxin Downregulation Reduces β-Catenin Levels and Shifts Hematopoietic Differentiation towards Myeloid Lineage In Vitro
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.