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 Rothamel; Adriana 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

doi:10.1038/ni.2587

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

158 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 γ^δ 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 language	English
Pages (from-to)	633-643
Number of pages	11
Journal	Nature Immunology
Volume	14
Issue number	6
DOIs	https://doi.org/10.1038/ni.2587
State	Published - Jun 2013
Externally published	Yes

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Jojic, V., Shay, T., Sylvia, K., Zuk, O., Sun, X., Kang, J., Regev, A., Koller, D., Best, A. J., Knell, J., Goldrath, A., Cohen, N., Brennan, P., Brenner, M., Kim, F., Rao, T. N., Wagers, A., Heng, T., Ericson, J., ... Turley, S. (2013). Identification of transcriptional regulators in the mouse immune system. Nature Immunology, 14(6), 633-643. https://doi.org/10.1038/ni.2587

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title = "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 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.",

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

year = "2013",

month = jun,

doi = "10.1038/ni.2587",

language = "אנגלית",

volume = "14",

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Jojic, V, Shay, T, Sylvia, K, Zuk, O, Sun, X, Kang, J, Regev, A, Koller, D, Best, AJ, Knell, J, Goldrath, A, Cohen, N, Brennan, P, Brenner, M, Kim, F, Rao, TN, Wagers, A, Heng, T, Ericson, J, Rothamel, K, Ortiz-Lopez, A, Mathis, D, Benoist, C, Bezman, NA, Sun, JC, Min-Oo, G, Kim, CC, Lanier, LL, Miller, J, Brown, B, Merad, M, Gautier, EL, Jakubzick, C, Randolph, GJ, Monach, P, Blair, DA, Dustin, ML, Shinton, SA, Hardy, RR, Laidlaw, D, Collins, J, Gazit, R, Rossi, DJ, Malhotra, N, Kreslavsky, T, Fletcher, A, Elpek, K, Bellemare-Pelletier, A, Malhotra, D & Turley, S 2013, 'Identification of transcriptional regulators in the mouse immune system', Nature Immunology, vol. 14, no. 6, pp. 633-643. https://doi.org/10.1038/ni.2587

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AU - Shay, Tal

AU - Sylvia, Katelyn

AU - Zuk, Or

AU - Sun, Xin

AU - Kang, Joonsoo

AU - Regev, Aviv

AU - Koller, Daphne

AU - Best, Adam J.

AU - Knell, Jamie

AU - Goldrath, Ananda

AU - Cohen, Nadia

AU - Brennan, Patrick

AU - Brenner, Michael

AU - Kim, Francis

AU - Rao, Tata Nageswara

AU - Wagers, Amy

AU - Heng, Tracy

AU - Ericson, Jeffrey

AU - Rothamel, Katherine

AU - Ortiz-Lopez, Adriana

AU - Mathis, Diane

AU - Benoist, Christophe

AU - Bezman, Natalie A.

AU - Sun, Joseph C.

AU - Min-Oo, Gundula

AU - Kim, Charlie C.

AU - Lanier, Lewis L.

AU - Miller, Jennifer

AU - Brown, Brian

AU - Merad, Miriam

AU - Gautier, Emmanuel L.

AU - Jakubzick, Claudia

AU - Randolph, Gwendalyn J.

AU - Monach, Paul

AU - Blair, David A.

AU - Dustin, Michael L.

AU - Shinton, Susan A.

AU - Hardy, Richard R.

AU - Laidlaw, David

AU - Collins, Jim

AU - Gazit, Roi

AU - Rossi, Derrick J.

AU - Malhotra, Nidhi

AU - Kreslavsky, Taras

AU - Fletcher, Anne

AU - Elpek, Kutlu

AU - Bellemare-Pelletier, Angelique

AU - Malhotra, Deepali

AU - Turley, Shannon

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AB - 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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Identification of transcriptional regulators in the mouse immune system

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