Identification of transcriptional regulators in the mouse immune system

被引：154

作者：

Jojic, Vladimir ^{[1
]}

Shay, Tal ^{[2
]}

Sylvia, Katelyn ^{[3
]}

Zuk, Or ^{[2
]}

Sun, Xin ^{[4
]}

Kang, Joonsoo ^{[3
]}

Regev, Aviv ^{[2
,5
]}

Koller, Daphne

机构：

[1] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA USA

[3] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA

[4] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA

[5] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA USA

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 06期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

DENDRITIC CELLS; T-CELLS; DIFFERENTIAL EXPRESSION; LINEAGE COMMITMENT; GENE-EXPRESSION; HEMATOPOIESIS; DIVERSITY; PROFILES; NETWORKS;

D O I：

10.1038/ni.2587

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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 gamma delta 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.

引用

页码：633 / +

页数：15

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