Skip to main content

The Ascano Laboratory

Identification of transcriptional regulators in the mouse immune system.

AUTHORS

Jojic VVladimir , Shay T Tal , Sylvia K Katelyn , Zuk O Or , Sun X Xin , Kang J Joonsoo , Regev A Aviv , Koller D Daphne , , Best AJ Adam J , Knell J Jamie , Goldrath A Ananda , Joic V Vladimir , Koller D Daphne , Shay T Tal , Regev A Aviv , Cohen N Nadia , Brennan P Patrick , Brenner M Michael , Kim F Francis , Rao TN Tata Nageswara , Wagers A Amy , Heng T Tracy , Ericson J Jeffrey , Rothamel K Katherine , Ortiz-Lopez A Adriana , Mathis D Diane , Benoist C Christophe , Bezman NA Natalie A , Sun JC Joseph C , Min-Oo G Gundula , Kim CC Charlie C , Lanier LL Lewis L , Miller J Jennifer , Brown B Brian , Merad M Miriam , Gautier EL Emmanuel L , Jakubzick C Claudia , Randolph GJ Gwendalyn J , Monach P Paul , Blair DA David A , Dustin ML Michael L , Shinton SA Susan A , Hardy RR Richard R , Laidlaw D David , Collins J Jim , Gazit R Roi , Rossi DJ Derrick J , Malhotra N Nidhi , Sylvia K Katelyn , Kang J Joonsoo , Kreslavsky T Taras , Fletcher A Anne , Elpek K Kutlu , Bellemarte-Pelletier A Angelique , Malhotra D Deepali , Turley S Shannon . Nature immunology. 2013 6 ; 14(6). 633-43

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.

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.

Leave a Response