The evolving metabolic landscape of chromatin biology and epigenetics

Nature Reviews Genetics, Год журнала: 2020, Номер 21(12), С. 737 - 753

Опубликована: Сен. 9, 2020

Язык: Английский

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Physiological Signaling Functions of Reactive Oxygen Species in Stem Cells: From Flies to Man

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Авг. 6, 2021

Reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, are generated as byproducts of oxidative phosphorylation in the mitochondria or via cell signaling-induced NADPH oxidases cytosol. In recent two decades, a plethora studies established that elevated ROS levels by eustress crucial physiological mediators many cellular developmental processes. this review, we discuss mechanisms generation regulation, current understanding functions maintenance adult embryonic stem cells, well process reprogramming to pluripotent state. Recently discovered cell-non-autonomous mediated growth factors for controlling differentiation immune response Drosophila . Importantly, may allow deciphering analogous processes human, which could potentially lead development novel therapeutic approaches ROS-associated diseases treatment.

Язык: Английский

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H3K18 lactylation marks tissue-specific active enhancers

Genome biology, Год журнала: 2022, Номер 23(1)

Опубликована: Окт. 3, 2022

Язык: Английский

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Piezoelectric hydrogel for treatment of periodontitis through bioenergetic activation

Bioactive Materials, Год журнала: 2024, Номер 35, С. 346 - 361

Опубликована: Фев. 14, 2024

The impaired differentiation ability of resident cells and disordered immune microenvironment in periodontitis pose a huge challenge for bone regeneration. Herein, we construct piezoelectric hydrogel to rescue the osteogenic capability rebuild regenerative through bioenergetic activation. Under local mechanical stress, generated piezopotential that initiates inflammatory periodontal ligament stem (PDLSCs) via modulating energy metabolism promoting adenosine triphosphate (ATP) synthesis. Moreover, it also reshapes an anti-inflammatory pro-regenerative niche switching M1 macrophages M2 phenotype. synergy tilapia gelatin stimulation enhances situ regeneration defects rats. These findings pave new pathway treating other immune-related stimulation-enabled modulation immunomodulation.

Язык: Английский

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Hallmarks of totipotent and pluripotent stem cell states

Cell stem cell, Год журнала: 2024, Номер 31(3), С. 312 - 333

Опубликована: Фев. 20, 2024

Though totipotency and pluripotency are transient during early embryogenesis, they establish the foundation for development of all mammals. Studying these in vivo has been challenging due to limited access ethical constraints, particularly humans. Recent progress led diverse culture adaptations epiblast cells vitro form totipotent pluripotent stem cells, which not only deepen our understanding embryonic but also serve as invaluable resources animal reproduction regenerative medicine. This review delves into hallmarks shedding light on their key molecular functional features.

Язык: Английский

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Single nucleus transcriptome and chromatin accessibility of postmortem human pituitaries reveal diverse stem cell regulatory mechanisms

Cell Reports, Год журнала: 2022, Номер 38(10), С. 110467 - 110467

Опубликована: Март 1, 2022

Despite their importance in tissue homeostasis and renewal, human pituitary stem cells (PSCs) are incompletely characterized. We describe a single nucleus RNA-seq ATAC-seq resource from pediatric, adult, aged postmortem pituitaries (snpituitaryatlas.princeton.edu) characterize cell-type-specific gene expression chromatin accessibility programs for all major cell lineages. identify uncommitted PSCs, committing progenitor cells, sex differences. Pseudotime trajectory analysis indicates that early-life PSCs distinct the other age groups. Linear modeling of same-cell multiome data identifies regulatory domain sites transcription factors significantly associated with compared types within PSCs. deterministic mechanisms contribute to heterogeneous marker These findings lineages reveal diverse regulating key PSC genes type identity.

Язык: Английский

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Molecular Mechanisms Underlying Pluripotency and Self-Renewal of Embryonic Stem Cells

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8386 - 8386

Опубликована: Май 7, 2023

Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of blastocyst. ESCs have two distinctive properties: ability to proliferate indefinitely, a feature referred as "self-renewal", and differentiate into different types, peculiar characteristic known "pluripotency". Self-renewal pluripotency finely orchestrated by precise external internal networks including epigenetic modifications, transcription factors, signaling pathways, histone modifications. In this systematic review, we examine main molecular mechanisms that sustain self-renewal in both murine human ESCs. Moreover, discuss latest literature on naïve pluripotency.

Язык: Английский

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Alpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives

Experimental Gerontology, Год журнала: 2023, Номер 175, С. 112154 - 112154

Опубликована: Март 20, 2023

Aging is a natural process that determined by functional decline in cells and tissues as organisms are growing old, resulting an increase at risk of disease death. To this end, many efforts have been made to control aging lifespan healthspan. These led the discovery several anti-aging drugs compounds such rapamycin metformin. Recently, alpha-ketoglutarate (AKG) has introduced potential metabolite can functions organisms, thereby increases longevity improves Unlike other synthetic drugs, AKG one metabolites tricarboxylic acid (TCA) cycle, also known Krebs synthesized body. It plays crucial role cell energy metabolism, amino acid/protein synthesis, epigenetic regulation, stemness differentiation, fertility reproductive health, cancer behaviors. exerts its effects through different mechanisms inhibiting mTOR ATP-synthase, modulating DNA histone demethylation reducing ROS formation. Herein, we summarize recent findings AKG-related healthspan studies discuss associated molecular involved increasing longevity, improving reproduction, stem behavior. We promises limitations for delaying applications.

Язык: Английский

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The Metabolic Changes between Monolayer (2D) and Three-Dimensional (3D) Culture Conditions in Human Mesenchymal Stem/Stromal Cells Derived from Adipose Tissue

Cells, Год журнала: 2023, Номер 12(1), С. 178 - 178

Опубликована: Янв. 1, 2023

One of the key factors that may influence therapeutic potential mesenchymal stem/stromal cells (MSCs) is their metabolism. The switch between mitochondrial respiration and glycolysis can be affected by many factors, including oxygen concentration spatial form culture. This study compared metabolic features adipose-derived (ASCs) dedifferentiated fat (DFATs) cultivated as monolayer or spheroid culture under 5% O2 (physiological normoxia) impact on MSCs abilities.We observed cultured spheroids had a slightly lower viability reduced proliferation rate but higher expression stemness-related transcriptional to in monolayer. three-dimensional increased mtDNA content, consumption (OCR) extracellular acidification (ECAR), especially DFATs-3D population. DFATs also demonstrated levels Complex V proteins rates ATP production. Moreover, reactive species intracellular lactic acid were found 3D culture.Our results suggest reconfiguration accompanies transition from 2D processes both become more active. Intensified metabolism might associated with demand for energy, which needed maintain pluripotency genes stemness state.

Язык: Английский

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Patient-derived cornea organoid model to study metabolomic characterization of rare disease: aniridia-associated keratopathy

BMC Ophthalmology, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 10, 2025

Aniridia is a rare panocular disease caused by gene mutation in the PAX6, which essential for eye development. inherited an autosomal dominant manner, but its phenotype can vary significantly among individuals with same mutation. Animal models, such as drosophila, zebrafish, and rodents, have been used to study aniridia through Pax6 deletions. Recently, patient-derived limbal epithelial stem cells (LESCs) human-induced pluripotent (hiPSCs) model vitro, providing new insights into therapeutic strategies. In this study, corneal organoids were generated from hiPSCs derived patients three different PAX6 nonsense mutations, allowing detailed comparison between diseased healthy control models. These structurally mimicked human cornea investigate histologic metabolomic differences aniridia-derived samples. Untargeted analysis revealed significant metabolic wild-type (WT) aniridia-associated keratopathy (AAK) hiPSCs. Further profiling at time points demonstrated distinct shifts, amino acid metabolism pathways being consistently enriched AAK organoids. This emphasizes profound impact of mutations on metabolism, particularly biosynthesis energy pathways.

Язык: Английский

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