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

Vikas Malik; Xin Huang; Hongwei Zhou; Rebecca Bojar; Rajesh Kumar Soni; Donald W Landry; Sanja Jelic; Jianlong Wang

doi:10.1016/j.isci.2025.112510

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

iScience. 2025 Apr 22;28(5):112510. doi: 10.1016/j.isci.2025.112510. eCollection 2025 May 16.

Authors

Vikas Malik¹, Xin Huang¹, Hongwei Zhou¹, Rebecca Bojar², Rajesh Kumar Soni³, Donald W Landry⁴, Sanja Jelic⁵, Jianlong Wang¹

Affiliations

¹ Department 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.
² Barnard College, Columbia University, New York, NY 10027, USA.
³ Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
⁴ Division 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, USA.
⁵ Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

Abstract

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.

Keywords: Neuroscience; Omics; Stem cells research.

Abstract

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