Identification of transcriptional regulators in the mouse immune system.

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...

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Main Authors: Jojic, V, Shay, T, Sylvia, K, Zuk, O, Sun, X, Kang, J, Regev, A, Koller, D, Best, A, Knell, J, Goldrath, A, Joic, V, Cohen, N, Brennan, P, Brenner, M, Kim, F, Rao, T, Wagers, A, Heng, T, Ericson, J, Rothamel, K, Ortiz-Lopez, A
Format: Journal article
Language:English
Published: 2013
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author Jojic, V
Shay, T
Sylvia, K
Zuk, O
Sun, X
Kang, J
Regev, A
Koller, D
Best, A
Knell, J
Goldrath, A
Joic, V
Koller, D
Shay, T
Regev, A
Cohen, N
Brennan, P
Brenner, M
Kim, F
Rao, T
Wagers, A
Heng, T
Ericson, J
Rothamel, K
Ortiz-Lopez, A
author_facet Jojic, V
Shay, T
Sylvia, K
Zuk, O
Sun, X
Kang, J
Regev, A
Koller, D
Best, A
Knell, J
Goldrath, A
Joic, V
Koller, D
Shay, T
Regev, A
Cohen, N
Brennan, P
Brenner, M
Kim, F
Rao, T
Wagers, A
Heng, T
Ericson, J
Rothamel, K
Ortiz-Lopez, A
author_sort Jojic, V
collection OXFORD
description 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.
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spelling oxford-uuid:85efb74a-5deb-4746-8775-a92392adf2622022-03-26T22:00:52ZIdentification of transcriptional regulators in the mouse immune system.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:85efb74a-5deb-4746-8775-a92392adf262EnglishSymplectic Elements at Oxford2013Jojic, VShay, TSylvia, KZuk, OSun, XKang, JRegev, AKoller, DBest, AKnell, JGoldrath, AJoic, VKoller, DShay, TRegev, ACohen, NBrennan, PBrenner, MKim, FRao, TWagers, AHeng, TEricson, JRothamel, KOrtiz-Lopez, AThe 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.
spellingShingle Jojic, V
Shay, T
Sylvia, K
Zuk, O
Sun, X
Kang, J
Regev, A
Koller, D
Best, A
Knell, J
Goldrath, A
Joic, V
Koller, D
Shay, T
Regev, A
Cohen, N
Brennan, P
Brenner, M
Kim, F
Rao, T
Wagers, A
Heng, T
Ericson, J
Rothamel, K
Ortiz-Lopez, A
Identification of transcriptional regulators in the mouse immune system.
title Identification of transcriptional regulators in the mouse immune system.
title_full Identification of transcriptional regulators in the mouse immune system.
title_fullStr Identification of transcriptional regulators in the mouse immune system.
title_full_unstemmed Identification of transcriptional regulators in the mouse immune system.
title_short Identification of transcriptional regulators in the mouse immune system.
title_sort identification of transcriptional regulators in the mouse immune system
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