Multiomics Evaluation of Human iPSCs and iPSC-Derived Neurons

Journal of Proteome Research, Год журнала: 2024, Номер 23(8), С. 3149 - 3160

Опубликована: Фев. 28, 2024

Human induced pluripotent stem cells (iPSCs) can be differentiated into neurons, providing living human neurons to model brain diseases. However, it is unclear how different types of molecules work together regulate cell and neuron biology in healthy disease states. In this study, we conducted integrated proteomics, lipidomics, metabolomics analyses with confident identification, accurate quantification, reproducible measurements compare the molecular profiles iPSCs iPSC-derived neurons. Proteins, lipids, metabolites related mitosis, DNA replication, pluripotency, glycosphingolipids, energy metabolism were highly enriched iPSCs, whereas synaptic proteins, neurotransmitters, polyunsaturated fatty acids, cardiolipins, axon guidance pathways Mutations GRN gene lead deficiency progranulin (PGRN) protein, which has been associated various neurodegenerative Using multiomics platform, evaluated impact PGRN on at whole-cell level. Proteomics, implicated PGRN's roles neuroinflammation, purine metabolism, neurite outgrowth, revealing commonly altered projection, dysfunction, metabolism. Multiomics data sets also pointed toward same hypothesis that seem more susceptible loss compared consistent neurological symptoms cognitive impairment from patients carrying inherited mutations.

Язык: Английский

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Blood-derived factors to brain communication in brain diseases

Science Bulletin, Год журнала: 2024, Номер 69(22), С. 3618 - 3632

Опубликована: Сен. 20, 2024

Brain diseases, mainly including acute brain injuries, neurodegenerative and mental disorders, have posed a significant threat to human health worldwide. Due the limited regenerative capability existence of blood-brain barrier, was previously thought be separated from rest body. Currently, various cross-talks between central nervous system peripheral organs been widely described, brain-gut axis, brain-liver brain-skeletal muscle brain-bone axis. Moreover, several lines evidence indicate that leveraging systemic biology intervention approaches, but not lifestyle interventions, exercise, diet, blood administration, immune responses, demonstrated influence on progress prognosis diseases. The advancement innovative proteomic transcriptomic technologies has enriched our understanding nuanced interplay An array novel or underappreciated blood-derived factors identified play pivotal roles in mediating these communications. In this review, we provide comprehensive summary blood-to-brain communication following Special attention is given instrumental role signals, positing them as contributors complex process insights presented here aim bridge current knowledge gaps inspire therapeutic strategies for

Язык: Английский

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Causal relationships between blood lipids and major psychiatric disorders: Univariable and multivariable mendelian randomization analysis

BMC Medical Genomics, Год журнала: 2023, Номер 16(1)

Опубликована: Окт. 18, 2023

Whether the positive associations of blood lipids with psychiatric disorders are causal is uncertain. We conducted this two-sample Mendelian randomization (MR) analysis to comprehensively investigate disorders.Univariable and multivariable models were established for MR analyses. Inverse variance-weighted (IVW) was employed as main approach; weighted median MR-Egger used sensitivity methods. The possibility violating assumptions evaluated utilizing several analyses, including heterogeneity statistics, horizontal pleiotropy single SNP analysis, leave-one-out MR-PRESSO analysis. As instrumental variables, we screened 362 independent single-nucleotide polymorphisms (SNP) related from a recent genome-wide association study involving 76,627 individuals European ancestry, significance level p < 5 × 10- 8. Summary-level information six extracted Psychiatric Genomics Consortium Alzheimer Disease Genetics Consortium.We observed eight significant in univariable four which corroborated by (MVMR) modified other three lipid traits: high-density lipoprotein cholesterol (HDL-C) risk PTSD (OR = 0.91, 95% CI 0.85-0.97, 0.002) AD 0.79, 0.71-0.88, 0.001) triglycerides (TG) MDD 1.02, 1.003-1.03, 0.01) panic disorder 0.83, 0.74-0.92, 0.001). In addition, not MVMR after adjustment total (TC) PTSD, low-density (LDL-C) TG AD.Our results show that may be manner. This shows abnormal levels act reliable biomarker suitable targets their prevention treatment.

Язык: Английский

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Lipid organization and turnover in the plasma membrane of human differentiating neural progenitor cells revealed by time-of-flight secondary ion mass spectrometry imaging

Talanta, Год журнала: 2024, Номер 272, С. 125762 - 125762

Опубликована: Фев. 14, 2024

Membrane lipids have been known to influence multiple signalling and cellular processes. Dysregulation of at the neuronal membrane is connected a significant alteration brain function morphology, leading diseases neurodegeneration. Understanding lipid composition turnover will provide insight into molecular events underlying regulatory effects these biomolecules in system. In this study, we aimed characterize plasma human neural progenitor cells (NPCs) an early differentiation stage midbrain neurons using ToF-SIMS imaging. Lipid native was explored, followed by examination different isotopically labelled precursors, including 13C-choline, 13C-lauric acid, 15N-linoleic, 13C-stearic. Our results showed that differentiating NPCs contain high abundance ceramides, glycerophosphoserines, neutral glycosphingolipids, diradylglycerols, glycerophosphocholines membrane. addition, precursors were found incorporate which are specific for short- or long-carbon chains, unsaturation saturation precursors. The structure reflects status NPCs, it can be altered significantly particular precursor. study illustrates potential imaging elucidate complex processes providing -rich information single cell level.

Язык: Английский

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An exploratory study on lipidomic profiles in a cohort of individuals with posttraumatic stress disorder

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июль 2, 2024

Abstract Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women PTSD at twice the rate of men, despite greater exposure in men. Lipids and their metabolites (lipidome) regulate a myriad key biological processes pathways such as membrane integrity, oxidative stress, neuroinflammation brain by maintaining neuronal connectivity homeostasis. In this study, we analyzed lipidome 40 adults with trauma-exposed non-PTSD individuals (n = 20/sex/condition; 19–39 years old). Plasma samples were for lipidomics using Quadrupole Time-of-Flight (QToF) mass spectrometry. Additionally, ~ 90 measures collected, on sleep, mental physical health indices. Poorer sleep quality was associated severity both sexes. The analysis identified total 348 quantifiable known lipid 1951 are yet unknown; part 13 subclasses. After adjusting BMI quality, PTSD, only one subclass, phosphatidylethanolamine (PE) altered, whereas, men 9 out subclasses altered compared to respectively. Severe 22% 5% women, Of changed metabolites, 0.5% (2 PEs cholesterol) common between PTSD. Several sphingomyelins, PEs, ceramides, triglycerides increased severe correlations ceramide cholesterol systolic blood pressure dependent upon sex status. Alterations ceramides linked cardiac metabolic function humans. Thus, disturbed higher body may have contributed changes found

Язык: Английский

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