Article

Overexpression of Snai3 suppresses lymphoid- and enhances myeloid-cell differentiation.

Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
European Journal of Immunology (Impact Factor: 4.52). 04/2012; 42(4):1038-43. DOI: 10.1002/eji.201142193
Source: PubMed

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.

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    • "In support of this conclusion, using a Snai3-EYFP transgenic mouse model, Snai3 expression was confirmed to be constrained to skeletal muscle and thymus and not to EMT sites [28]. Furthermore, Snai3 null mice do not exhibit any obvious phenotype including no evident defect in T lymphocyte development [28], while SNAI3 transduction in hematopoietic stem cells was previously shown to favor their commitment into the myeloid lineage at the expense of the lymphoid lineage [29]. Lack of phenotype has recently been explained by demonstrating that SNAIL2 and SNAIL3 display redundant functions in regards to B and T cell differentiation. "
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    • "After removing Ponceau staining via TBS-T washing, blots were blocked in 5% NFDM/TBS-T for 1 hour at room temperature. Blots were then probed at 4° C overnight with the following primary antibodies at the indicated dilutions: Snai1 (Santa Cruz, sc-10432, 1:250), Snai2 (Santa Cruz, sc-10436, 1:100), Snai3 (Harlan Bioproducts, P070240, 1:250) [21], and β-actin (Sigma, A2066, 1:10,000). The next day, blots were washed with TBS-T and incubated for 2 hours at room temperature with the following secondary antibodies: peroxidase-conjugated bovine anti-goat (Jackson ImmunoResearch, 805-035-180, 1:10,000) or peroxidase-conjugated goat anti-rabbit (Bio-Rad, 170-6515, 1:10,000). "
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