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 W Goldrath; Nadia R Cohen; Patrick J Brennan; Michael B Brenner; Francis S Kim; Tata N Rao; Amy Wagers; Tracy S P Heng; Jeffrey A Ericson; Katherine Rothamel; Andrianna Ortiz-Lopez; Diane Mathis; Christophe Benoist; Natalie A Bezman; Joseph C Sun; Gundula Min-Oo; Charlie C Kim; Lewis L Lanier; Jennifer C Miller; Brian D Brown; Miriam Merad; Emmanuel L Gautier; Claudia V Jakubzick; Gwendalyn J Randolph; Paul Monach; David A Blair; Michael L Dustin; Susan A Shinton; Richard R Hardy; David H Laidlaw; Jim J Collins; Roi Gazit; Derrick J Rossi; Nidhi Malhotra; Taras Kreslavsky; Anne Fletcher; Kutlu G Elpek; Angelique Bellemare-Pelletier; Deepali Malhotra; Shannon J 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 W Goldrath, Nadia R Cohen, Patrick J Brennan, Michael B Brenner, Francis S Kim, Tata N Rao, Amy Wagers, Tracy S P Heng, Jeffrey A Ericson, Katherine RothamelAndrianna Ortiz-Lopez, Diane Mathis, Christophe Benoist, Natalie A Bezman, Joseph C Sun, Gundula Min-Oo, Charlie C Kim, Lewis L Lanier, Jennifer C Miller, Brian D Brown, Miriam Merad, Emmanuel L Gautier, Claudia V Jakubzick, Gwendalyn J Randolph, Paul Monach, David A Blair, Michael L Dustin, Susan A Shinton, Richard R Hardy, David H Laidlaw, Jim J Collins, Roi Gazit, Derrick J Rossi, Nidhi Malhotra, Taras Kreslavsky, Anne Fletcher, Kutlu G Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon J Turley

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

148 Citations (Scopus)

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 gammadelta 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
Publication status	Published - 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. W., Cohen, N. R., Brennan, P. J., Brenner, M. B., Kim, F. S., Rao, T. N., Wagers, A., Heng, T. S. P., Ericson, J. A., ... Turley, S. J. (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 gammadelta 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 Goldrath, {Ananda W} and Cohen, {Nadia R} and Brennan, {Patrick J} and Brenner, {Michael B} and Kim, {Francis S} and Rao, {Tata N} and Amy Wagers and Heng, {Tracy S P} and Ericson, {Jeffrey A} and Katherine Rothamel and Andrianna 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 Miller, {Jennifer C} and Brown, {Brian D} and Miriam Merad and Gautier, {Emmanuel L} and Jakubzick, {Claudia V} and Randolph, {Gwendalyn J} and Paul Monach and Blair, {David A} and Dustin, {Michael L} and Shinton, {Susan A} and Hardy, {Richard R} and Laidlaw, {David H} and Collins, {Jim J} and Roi Gazit and Rossi, {Derrick J} and Nidhi Malhotra and Taras Kreslavsky and Anne Fletcher and Elpek, {Kutlu G} and Angelique Bellemare-Pelletier and Deepali Malhotra and Turley, {Shannon J}",

year = "2013",

doi = "10.1038/ni.2587",

language = "English",

volume = "14",

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journal = "Nature Immunology",

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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, AW, Cohen, NR, Brennan, PJ, Brenner, MB, Kim, FS, Rao, TN, Wagers, A, Heng, TSP, Ericson, JA, Rothamel, K, Ortiz-Lopez, A, Mathis, D, Benoist, C, Bezman, NA, Sun, JC, Min-Oo, G, Kim, CC, Lanier, LL, Miller, JC, Brown, BD, Merad, M, Gautier, EL, Jakubzick, CV, Randolph, GJ, Monach, P, Blair, DA, Dustin, ML, Shinton, SA, Hardy, RR, Laidlaw, DH, Collins, JJ, Gazit, R, Rossi, DJ, Malhotra, N, Kreslavsky, T, Fletcher, A, Elpek, KG, Bellemare-Pelletier, A, Malhotra, D & Turley, SJ 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

TY - JOUR

T1 - Identification of transcriptional regulators in the mouse immune system

AU - Jojic, Vladimir

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 W

AU - Cohen, Nadia R

AU - Brennan, Patrick J

AU - Brenner, Michael B

AU - Kim, Francis S

AU - Rao, Tata N

AU - Wagers, Amy

AU - Heng, Tracy S P

AU - Ericson, Jeffrey A

AU - Rothamel, Katherine

AU - Ortiz-Lopez, Andrianna

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 C

AU - Brown, Brian D

AU - Merad, Miriam

AU - Gautier, Emmanuel L

AU - Jakubzick, Claudia V

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 H

AU - Collins, Jim J

AU - Gazit, Roi

AU - Rossi, Derrick J

AU - Malhotra, Nidhi

AU - Kreslavsky, Taras

AU - Fletcher, Anne

AU - Elpek, Kutlu G

AU - Bellemare-Pelletier, Angelique

AU - Malhotra, Deepali

AU - Turley, Shannon J

PY - 2013

Y1 - 2013

N2 - 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 gammadelta 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.

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 gammadelta 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/23624555

U2 - 10.1038/ni.2587

DO - 10.1038/ni.2587

M3 - Article

VL - 14

SP - 633

EP - 643

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 6

ER -

Identification of transcriptional regulators in the mouse immune system

Abstract

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