Overexpression of Snai3 suppresses lymphoid- and enhances myeloid-cell differentiation.
ABSTRACT The altered expression of transcription factors in hematopoietic stem cells and their subsequent lineages can alter the development of lymphoid and myeloid lineages. The role of the transcriptional repressor Snai3 protein in the derivation of cells of the hemato-poietic system was investigated. Snai3 is expressed in terminal T-cell and myeloid lineages, therefore, we chose to determine if expressing Snai3 in the early stages of hematopoietic development would influence cell-lineage determination. Expression of Snai3 by retroviral transduction of hematopoietic stem cells using bone marrow chimera studies demonstrated a block in lymphoid-cell development and enhanced expansion of myeloid-lineage cells. Analysis of Snai3-expressing hematopoietic precursor cells showed normal numbers of immature cells, but a block in the development of cells committed to lymphoid lineages. These data indicate that the overexpression of Snai3 does alter bone marrow cell development and that the identification of genes whose expression is altered by the presence of Snai3 would aid in our understanding of these developmental pathways.
Full-textDOI: · Available from: Timothy John Dahlem, Mar 17, 2014
Click to see the full-text of:
Article: Overexpression of Snai3 suppresses lymphoid- and enhances myeloid-cell differentiation.
SourceAvailable from: Peter D Pioli[Show abstract] [Hide abstract]
ABSTRACT: Coordinated gene expression is crucial in facilitating proper lymphoid cell development and function. The precise patterns of gene expression during B and T cell development are regulated through a complex interplay between a multitude of transcriptional regulators, both activators and repressors. We have recently identified the Snail family of transcription factors as playing significant and overlapping roles in lymphoid cell development in that deletion of both Snai2 and Snai3 was required to fully impact the generation of mature T and B cells. Analyses using compound heterozygote animals further demonstrated that Snai2 and Snai3 were partially haplo-sufficient and relatively equivalent in their ability to preserve B cell generation in the bone marrow. In this review, we summarize studies elucidating the role(s) of the Snail family in hematopoiesis with a focus on lymphoid cell development. Using the Snail family as an example, we discuss the concepts of functional redundancy and strategies employed to assay transcription factor families for "intra-member" compensation.Experimental hematology 03/2014; 42(6). DOI:10.1016/j.exphem.2014.03.002 · 2.81 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Purpose: Epithelial-mesenchymal transition (EMT) is crucial for tumor progression and metastasis. Snail family members, including Snail, Slug and Smuc, are the transcription factors that repress E-cadherin expression and induce epithelial-mesenchymal transition in some tumor tissues. In this study, the expression of snail family proteins in cervical squamous cancers was evaluated. Methods: A series of 144 samples, comprising 28 cases of normal cervical tissues and 116 cases of squamous cell carcinoma (SCC), were used for analysis. The expression of Snail, Slug, Smuc, E-cadherin and vimentin was assessed in the tissues by immunohistochemistry and was statistically analyzed by SPSS13.0. Results: The increase in nuclear expression of snail and smuc was associated with down-regulation of E-cadherin and up-regulation of vimentin. The nuclear expression of Snail and Smuc was positively associated with lymph node metastasis of the SCC, and the nuclear expression of Snail was also positively related with histological differentiation. In contrast, tumor size, histological differentiation, lymph node metastasis and stages of the SCC were not associated with the expression of Slug, cytpolasmic Smuc or cytoplasm levels of Snail. Conclusion: Snail and Smuc proteins, but not Slug, may contribute to the onset of EMT in SCC. Inhibiting the expression of Snail and Smuc might be a potential therapeutic target for the treatment of metastasis and invasion of cervical carcinomas.Clinical and investigative medicine. Medecine clinique et experimentale 01/2013; 36(4):E223. · 1.15 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: By fostering cell commitment to the epithelial-to-mesenchymal transition (EMT), SNAIL proteins endow cells with motility, thereby favoring the metastatic spread of tumor cells. Whether the phenotypic change additionally facilitates tumor initiation has never been addressed. Here we demonstrate that when a SNAIL protein is ectopically produced in non-transformed mammary epithelial cells, the cells are protected from anoikis and proliferate under low-adherence conditions: a hallmark of cancer cells. The three SNAIL proteins show unequal oncogenic potential, strictly correlating with their ability to promote EMT. SNAIL3 especially behaves as a poor EMT-inducer comforting the concept that the transcription factor functionally diverges from its two related proteins.PLoS ONE 03/2014; 9(3):e92254. DOI:10.1371/journal.pone.0092254 · 3.53 Impact Factor