Identification of transcriptional regulators in the mouse immune system

Vladimir Jojic, Tal Shay, Katelyn Sylvia, Or Zuk, Xin Sun, Joonsoo Kang, Aviv Regev, Daphne Koller, Adam J. Best, Jamie Knell, Ananda Goldrath, Nadia Cohen, Patrick Brennan, Michael Brenner, Francis Kim, Tata Nageswara Rao, Amy Wagers, Tracy Heng, Jeffrey Ericson, Katherine RothamelAdriana Ortiz-Lopez, Diane Mathis, Christophe Benoist, Natalie A. Bezman, Joseph C. Sun, Gundula Min-Oo, Charlie C. Kim, Lewis L. Lanier, Jennifer Miller, Brian Brown, Miriam Merad, Emmanuel L. Gautier, Claudia Jakubzick, Gwendalyn J. Randolph, Paul Monach, David A. Blair, Michael L. Dustin, Susan A. Shinton, Richard R. Hardy, David Laidlaw, Jim Collins, Roi Gazit, Derrick J. Rossi, Nidhi Malhotra, Taras Kreslavsky, Anne Fletcher, Kutlu Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon Turley

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)633-643
Number of pages11
JournalNature immunology
Volume14
Issue number6
DOIs
StatePublished - Jun 2013

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