Comparative transcriptomic rhythms in the mouse and human prefrontal cortex

IntroductionAlterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are alte...

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Main Authors: Jennifer N. Burns, Aaron K. Jenkins, Xiangning Xue, Kaitlyn A. Petersen, Kyle D. Ketchesin, Megan S. Perez, Chelsea A. Vadnie, Madeline R. Scott, Marianne L. Seney, George C. Tseng, Colleen A. McClung
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Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2024.1524615/full
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author Jennifer N. Burns
Jennifer N. Burns
Aaron K. Jenkins
Xiangning Xue
Kaitlyn A. Petersen
Kaitlyn A. Petersen
Kyle D. Ketchesin
Kyle D. Ketchesin
Megan S. Perez
Megan S. Perez
Chelsea A. Vadnie
Madeline R. Scott
Madeline R. Scott
Marianne L. Seney
Marianne L. Seney
George C. Tseng
Colleen A. McClung
Colleen A. McClung
author_facet Jennifer N. Burns
Jennifer N. Burns
Aaron K. Jenkins
Xiangning Xue
Kaitlyn A. Petersen
Kaitlyn A. Petersen
Kyle D. Ketchesin
Kyle D. Ketchesin
Megan S. Perez
Megan S. Perez
Chelsea A. Vadnie
Madeline R. Scott
Madeline R. Scott
Marianne L. Seney
Marianne L. Seney
George C. Tseng
Colleen A. McClung
Colleen A. McClung
author_sort Jennifer N. Burns
collection DOAJ
description IntroductionAlterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are altered in disease. However, investigation into the potential circadian mechanisms underlying these diseases in animal models must contend with the fact that the human PFC is highly evolved and specialized relative to that of rodents.MethodsHere, we use RNA sequencing to lay the groundwork for translational studies of molecular rhythms through a sex-specific, cross species comparison of transcriptomic rhythms between the mouse medial PFC (mPFC) and two subregions of the human PFC, the anterior cingulate cortex (ACC) and the dorsolateral PFC (DLPFC).ResultsWe find that while circadian rhythm signaling is conserved across species and subregions, there is a phase shift in the expression of core clock genes between the mouse mPFC and human PFC subregions that differs by sex. Furthermore, we find that the identity of rhythmic transcripts is largely unique between the mouse mPFC and human PFC subregions, with the most overlap (20%, 236 transcripts) between the mouse mPFC and the human ACC in females. Nevertheless, we find that basic biological processes are enriched for rhythmic transcripts across species, with key differences between regions and sexes.DiscussionTogether, this work highlights both the evolutionary conservation of transcriptomic rhythms and the advancement of the human PFC, underscoring the importance of considering cross-species differences when using animal models.
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spelling doaj-art-5fcc1eb2c140495080071f056cbf32e62025-01-13T06:10:46ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-01-011810.3389/fnins.2024.15246151524615Comparative transcriptomic rhythms in the mouse and human prefrontal cortexJennifer N. Burns0Jennifer N. Burns1Aaron K. Jenkins2Xiangning Xue3Kaitlyn A. Petersen4Kaitlyn A. Petersen5Kyle D. Ketchesin6Kyle D. Ketchesin7Megan S. Perez8Megan S. Perez9Chelsea A. Vadnie10Madeline R. Scott11Madeline R. Scott12Marianne L. Seney13Marianne L. Seney14George C. Tseng15Colleen A. McClung16Colleen A. McClung17Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United StatesTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA, United StatesTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United StatesTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United StatesTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, United StatesDavid O. Robbins Neuroscience Program, Department of Psychology, Ohio Wesleyan University, Delaware, OH, United StatesTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United StatesTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA, United StatesTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesCenter for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United StatesIntroductionAlterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are altered in disease. However, investigation into the potential circadian mechanisms underlying these diseases in animal models must contend with the fact that the human PFC is highly evolved and specialized relative to that of rodents.MethodsHere, we use RNA sequencing to lay the groundwork for translational studies of molecular rhythms through a sex-specific, cross species comparison of transcriptomic rhythms between the mouse medial PFC (mPFC) and two subregions of the human PFC, the anterior cingulate cortex (ACC) and the dorsolateral PFC (DLPFC).ResultsWe find that while circadian rhythm signaling is conserved across species and subregions, there is a phase shift in the expression of core clock genes between the mouse mPFC and human PFC subregions that differs by sex. Furthermore, we find that the identity of rhythmic transcripts is largely unique between the mouse mPFC and human PFC subregions, with the most overlap (20%, 236 transcripts) between the mouse mPFC and the human ACC in females. Nevertheless, we find that basic biological processes are enriched for rhythmic transcripts across species, with key differences between regions and sexes.DiscussionTogether, this work highlights both the evolutionary conservation of transcriptomic rhythms and the advancement of the human PFC, underscoring the importance of considering cross-species differences when using animal models.https://www.frontiersin.org/articles/10.3389/fnins.2024.1524615/fullcircadian rhythmstranscriptomicsprefrontal cortexmousehuman post mortem tissue
spellingShingle Jennifer N. Burns
Jennifer N. Burns
Aaron K. Jenkins
Xiangning Xue
Kaitlyn A. Petersen
Kaitlyn A. Petersen
Kyle D. Ketchesin
Kyle D. Ketchesin
Megan S. Perez
Megan S. Perez
Chelsea A. Vadnie
Madeline R. Scott
Madeline R. Scott
Marianne L. Seney
Marianne L. Seney
George C. Tseng
Colleen A. McClung
Colleen A. McClung
Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
Frontiers in Neuroscience
circadian rhythms
transcriptomics
prefrontal cortex
mouse
human post mortem tissue
title Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
title_full Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
title_fullStr Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
title_full_unstemmed Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
title_short Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
title_sort comparative transcriptomic rhythms in the mouse and human prefrontal cortex
topic circadian rhythms
transcriptomics
prefrontal cortex
mouse
human post mortem tissue
url https://www.frontiersin.org/articles/10.3389/fnins.2024.1524615/full
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