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Identification of transcriptional regulators in the mouse immune system
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Identification of transcriptional regulators in the mouse immune system
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Journal Article
Identification of transcriptional regulators in the mouse immune system
2013
Overview
The transcriptional circuitry that controls the differentiation of hematopoietic stem cells into cells of the immune system is only partially understood. Koller and colleagues use a computational algorithm to identify previously unknown differentiation stage–specific regulators of mouse hematopoiesis.
The differentiation of hematopoietic stem cells into cells of the immune system has been studied extensively in mammals, but the transcriptional circuitry that controls it is still only partially understood. Here, the Immunological Genome Project gene-expression profiles across mouse immune lineages allowed us to systematically analyze these circuits. To analyze this data set we developed Ontogenet, an algorithm for reconstructing lineage-specific regulation from gene-expression profiles across lineages. Using Ontogenet, we found differentiation stage–specific regulators of mouse hematopoiesis and identified many known hematopoietic regulators and 175 previously unknown candidate regulators, as well as their target genes and the cell types in which they act. Among the previously unknown regulators, we emphasize the role of ETV5 in the differentiation of γδ T cells. As the transcriptional programs of human and mouse cells are highly conserved, it is likely that many lessons learned from the mouse model apply to humans.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Analysis
/ Animals
/ Cell Differentiation - genetics
/ Cell Differentiation - immunology
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - immunology
/ Gene Expression Regulation - immunology
/ Gene Regulatory Networks - immunology
/ Humans
/ Mammals
/ Mice
/ Oligonucleotide Array Sequence Analysis
/ Receptors, Antigen, T-Cell, gamma-delta
/ Receptors, Antigen, T-Cell, gamma-delta - immunology
/ Receptors, Antigen, T-Cell, gamma-delta - metabolism
/ Repressor Proteins - genetics
/ Repressor Proteins - immunology
/ resource
/ T cells
/ Trans-Activators - immunology
/ Transcription Factors - genetics
/ Transcription Factors - immunology
