Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functions

Summary: Adequate sleep (AS) is vital for physiological functions, yet a third of US adults sleep less than recommended. While circadian rhythms regulate adult stem cell functions, the impact of insufficient sleep remains unclear. We previously completed a clinical trial in healthy women in a random...

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Main Authors: Vikas Malik, Xin Huang, Hongwei Zhou, Rebecca Bojar, Rajesh Kumar Soni, Donald W. Landry, Sanja Jelic, Jianlong Wang
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225007710
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author Vikas Malik
Xin Huang
Hongwei Zhou
Rebecca Bojar
Rajesh Kumar Soni
Donald W. Landry
Sanja Jelic
Jianlong Wang
author_facet Vikas Malik
Xin Huang
Hongwei Zhou
Rebecca Bojar
Rajesh Kumar Soni
Donald W. Landry
Sanja Jelic
Jianlong Wang
author_sort Vikas Malik
collection DOAJ
description Summary: Adequate sleep (AS) is vital for physiological functions, yet a third of US adults sleep less than recommended. While circadian rhythms regulate adult stem cell functions, the impact of insufficient sleep remains unclear. We previously completed a clinical trial in healthy women in a randomized crossover design of 6-week periods with AS or mildly restricted sleep (RS; 1.5 h less). Here, we performed metabolomic and proteomic profiling of plasma samples. RS induced a stress-like state, highlighted by ER stress, heat shock, ubiquitination proteins, and amino acid biosynthesis. RS was strongly linked to disrupted neural development. Treating neural stem cells (NSCs) derived from human embryonic stem cells with RS-enriched metabolites disrupted G1 cell cycle phase and impaired differentiation into neurons, astrocytes, and oligodendrocytes. Our findings reveal how mild RS, mimicking “real-life” conditions, disrupts NSC divisions and differentiation, highlighting the critical role of sleep in adult stem cell regulation and neural development.
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spelling doaj-art-ce0726b5078340fea9ba140c4a8d7de32025-08-20T01:49:08ZengElsevieriScience2589-00422025-05-0128511251010.1016/j.isci.2025.112510Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functionsVikas Malik0Xin Huang1Hongwei Zhou2Rebecca Bojar3Rajesh Kumar Soni4Donald W. Landry5Sanja Jelic6Jianlong Wang7Department of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USABarnard College, Columbia University, New York, NY 10027, USAProteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USADivision of Nephrology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York-Presbyterian/Columbia University Irving Medical Center, New York, NY 10032, USADivision of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USADepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Corresponding authorSummary: Adequate sleep (AS) is vital for physiological functions, yet a third of US adults sleep less than recommended. While circadian rhythms regulate adult stem cell functions, the impact of insufficient sleep remains unclear. We previously completed a clinical trial in healthy women in a randomized crossover design of 6-week periods with AS or mildly restricted sleep (RS; 1.5 h less). Here, we performed metabolomic and proteomic profiling of plasma samples. RS induced a stress-like state, highlighted by ER stress, heat shock, ubiquitination proteins, and amino acid biosynthesis. RS was strongly linked to disrupted neural development. Treating neural stem cells (NSCs) derived from human embryonic stem cells with RS-enriched metabolites disrupted G1 cell cycle phase and impaired differentiation into neurons, astrocytes, and oligodendrocytes. Our findings reveal how mild RS, mimicking “real-life” conditions, disrupts NSC divisions and differentiation, highlighting the critical role of sleep in adult stem cell regulation and neural development.http://www.sciencedirect.com/science/article/pii/S2589004225007710NeuroscienceStem cells researchOmics
spellingShingle Vikas Malik
Xin Huang
Hongwei Zhou
Rebecca Bojar
Rajesh Kumar Soni
Donald W. Landry
Sanja Jelic
Jianlong Wang
Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functions
iScience
Neuroscience
Stem cells research
Omics
title Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functions
title_full Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functions
title_fullStr Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functions
title_full_unstemmed Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functions
title_short Multiomics reveal biomolecular shifts and ER stress in sleep-restricted women affecting NSC functions
title_sort multiomics reveal biomolecular shifts and er stress in sleep restricted women affecting nsc functions
topic Neuroscience
Stem cells research
Omics
url http://www.sciencedirect.com/science/article/pii/S2589004225007710
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