Dataset Information

Identification of transcriptional regulators in the mouse immune system.

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 ?? 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.

SUBMITTER: Jojic V

PROVIDER: S-EPMC3690947 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of transcriptional regulators in the mouse immune system.

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

Nature immunology 20130428 6

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 ...[more]

PMID: 23624555

Similar Datasets

Project description:One of the great challenges in the post-genomic era is to decipher the underlying principles governing the dynamics of biological responses. As modulating gene expression levels is among the key regulatory responses of an organism to changes in its environment, identifying biologically relevant transcriptional regulators and their putative regulatory interactions with target genes is an essential step towards studying the complex dynamics of transcriptional regulation. We present an analysis that integrates various computational and biological aspects to explore the transcriptional regulation of systemic inflammatory responses through a human endotoxemia model. Given a high-dimensional transcriptional profiling dataset from human blood leukocytes, an elementary set of temporal dynamic responses which capture the essence of a pro-inflammatory phase, a counter-regulatory response and a dysregulation in leukocyte bioenergetics has been extracted. Upon identification of these expression patterns, fourteen inflammation-specific gene batteries that represent groups of hypothetically 'coregulated' genes are proposed. Subsequently, statistically significant cis-regulatory modules (CRMs) are identified and decomposed into a list of critical transcription factors (34) that are validated largely on primary literature. Finally, our analysis further allows for the construction of a dynamic representation of the temporal transcriptional regulatory program across the host, deciphering possible combinatorial interactions among factors under which they might be active. Although much remains to be explored, this study has computationally identified key transcription factors and proposed a putative time-dependent transcriptional regulatory program associated with critical transcriptional inflammatory responses. These results provide a solid foundation for future investigations to elucidate the underlying transcriptional regulatory mechanisms under the host inflammatory response. Also, the assumption that coexpressed genes that are functionally relevant are more likely to share some common transcriptional regulatory mechanism seems to be promising, making the proposed framework become essential in unravelling context-specific transcriptional regulatory interactions underlying diverse mammalian biological processes.

Dataset Information

Identification of transcriptional regulators in the mouse immune system.

Publications

Identification of transcriptional regulators in the mouse immune system.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets