Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression

Joseph R. Scarpa, Peng Jiang, Vance D. Gao, Karrie Fitzpatrick, Joshua Millstein, Christopher Olker, Anthony Gotter, Christopher J. Winrow, John J. Renger, Andrew Kasarskis*, Fred W. Turek, Martha H. Vitaterna

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J × 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Using publicly available transcriptomic datasets collected from sleep-deprived mice and patients with major depressive disorder (MDD), we identified three cortical gene networks altered by the sleep/wake state and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression, as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity–dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.

Original languageEnglish (US)
Article numbereaat1294
JournalScience Advances
Volume4
Issue number7
DOIs
StatePublished - Jul 25 2018

Fingerprint

Gene Regulatory Networks
Systems Analysis
Sleep
Depression
Major Depressive Disorder
Phenotype
Immediate-Early Genes
Sleep Deprivation
Gene Expression Profiling
Circadian Rhythm
Antidepressive Agents
Brain

ASJC Scopus subject areas

  • General

Cite this

Scarpa, Joseph R. ; Jiang, Peng ; Gao, Vance D. ; Fitzpatrick, Karrie ; Millstein, Joshua ; Olker, Christopher ; Gotter, Anthony ; Winrow, Christopher J. ; Renger, John J. ; Kasarskis, Andrew ; Turek, Fred W. ; Vitaterna, Martha H. / Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression. In: Science Advances. 2018 ; Vol. 4, No. 7.
@article{82de0062d1834f25b589db63d1fe86d3,
title = "Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression",
abstract = "To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J × 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Using publicly available transcriptomic datasets collected from sleep-deprived mice and patients with major depressive disorder (MDD), we identified three cortical gene networks altered by the sleep/wake state and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression, as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity–dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.",
author = "Scarpa, {Joseph R.} and Peng Jiang and Gao, {Vance D.} and Karrie Fitzpatrick and Joshua Millstein and Christopher Olker and Anthony Gotter and Winrow, {Christopher J.} and Renger, {John J.} and Andrew Kasarskis and Turek, {Fred W.} and Vitaterna, {Martha H.}",
year = "2018",
month = "7",
day = "25",
doi = "10.1126/sciadv.aat1294",
language = "English (US)",
volume = "4",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "7",

}

Scarpa, JR, Jiang, P, Gao, VD, Fitzpatrick, K, Millstein, J, Olker, C, Gotter, A, Winrow, CJ, Renger, JJ, Kasarskis, A, Turek, FW & Vitaterna, MH 2018, 'Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression', Science Advances, vol. 4, no. 7, eaat1294. https://doi.org/10.1126/sciadv.aat1294

Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression. / Scarpa, Joseph R.; Jiang, Peng; Gao, Vance D.; Fitzpatrick, Karrie; Millstein, Joshua; Olker, Christopher; Gotter, Anthony; Winrow, Christopher J.; Renger, John J.; Kasarskis, Andrew; Turek, Fred W.; Vitaterna, Martha H.

In: Science Advances, Vol. 4, No. 7, eaat1294, 25.07.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression

AU - Scarpa, Joseph R.

AU - Jiang, Peng

AU - Gao, Vance D.

AU - Fitzpatrick, Karrie

AU - Millstein, Joshua

AU - Olker, Christopher

AU - Gotter, Anthony

AU - Winrow, Christopher J.

AU - Renger, John J.

AU - Kasarskis, Andrew

AU - Turek, Fred W.

AU - Vitaterna, Martha H.

PY - 2018/7/25

Y1 - 2018/7/25

N2 - To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J × 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Using publicly available transcriptomic datasets collected from sleep-deprived mice and patients with major depressive disorder (MDD), we identified three cortical gene networks altered by the sleep/wake state and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression, as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity–dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.

AB - To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J × 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Using publicly available transcriptomic datasets collected from sleep-deprived mice and patients with major depressive disorder (MDD), we identified three cortical gene networks altered by the sleep/wake state and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression, as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity–dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.

UR - http://www.scopus.com/inward/record.url?scp=85050794721&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050794721&partnerID=8YFLogxK

U2 - 10.1126/sciadv.aat1294

DO - 10.1126/sciadv.aat1294

M3 - Article

C2 - 30050989

AN - SCOPUS:85050794721

VL - 4

JO - Science advances

JF - Science advances

SN - 2375-2548

IS - 7

M1 - eaat1294

ER -