The Mammalian Oocyte: A Central Hub for Cellular Reprogramming and Stemness

Stem Cells and Cloning Advances and Applications, Journal Year: 2025, Volume and Issue: Volume 18, P. 15 - 34

Published: Feb. 1, 2025

The mammalian oocyte is pivotal in reproductive biology, acting as a central hub for cellular reprogramming and stemness. It uniquely contributes half of the zygotic nuclear genome entirety mitochondrial genome, ensuring individual development health. Oocyte-mediated reprogramming, exemplified by transfer, resets somatic cell identity to achieve pluripotency has transformative potential regenerative medicine. This process critical understanding differentiation, improving assisted technologies, advancing cloning stem research. During fertilization, maternal-zygotic transition shifts developmental control from maternal factors activation, establishing totipotency. Oocytes also harbor that guide remodeling, epigenetic modifications, metabolic enabling early embryogenesis. Structures like mitochondria, lipid droplets, cytoplasmic lattices contribute energy production, molecular regulation, organization. Recent insights into components, such ooplasmic nanovesicles endolysosomal vesicular assemblies (ELVAS), highlight their roles maintaining homeostasis, protein synthesis, efficiency. By unraveling mechanisms inherent oocytes, we advance our cloning, therapy, highlighting valuable significance biology

Language: Английский

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Noncanonical inheritance of phenotypic information by protein amyloids

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(10), P. 1712 - 1724

Published: Sept. 2, 2024

Language: Английский

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Endosomal-lysosomal organellar assembly (ELYSA) structures coordinate lysosomal degradation systems through mammalian oocyte-to-embryo transition

Published: Jan. 31, 2025

Mouse oocytes undergo drastic changes in organellar composition and their activities during maturation from the germinal vesicle (GV) to meiosis II (MII) stage. After fertilization, embryo degrades parts of maternal components via lysosomal degradation systems, including autophagy endocytosis, as zygotic gene expression begins embryogenesis. Here, we demonstrate that endosomal-lysosomal organelles form large spherical assembly structures, termed ELYSAs, mouse oocytes. ELYSAs are observed GV oocytes, attaining sizes up 7–8 μm diameter MII comprise tubular-vesicular structures containing endosomes lysosomes along with cytosolic components. Most also positive for an regulator, LC3. These characteristics ELYSA resemble those ELVA (endolysosomal vesicular assemblies) identified independently. The signals V1-subunit vacuolar ATPase tends be detected on periphery localization increase gradually disassemble at 2-cell stage, leading further acidification organelles. findings suggest ELYSA/ELVA maintain activity a static state timely activation early development.

Language: Английский

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Mitophagy at the oocyte-to-zygote transition promotes species immortality

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract The quality of inherited mitochondria determines embryonic viability 1 , metabolic health during adulthood and future generation endurance. oocyte is the source all zygotic 2 mitochondrial under strict developmental regulation early oogenesis 3–5 . Yet, fully developed oocytes exhibit presence deleterious DNA (mtDNA) 6,7 dysfunction from high levels endogenous reactive oxygen species 8 exogenous toxicants 9 How prevent transmission damaged to zygotes unknown. Here we discover that onset oocyte-to-zygote transition (OZT) developmentally triggers a robust rapid mitophagy event term at OZT (MOZT). We show MOZT requires fragmentation, activation macroautophagy system receptor FUNDC1, but not prevalent factors PINK1 BNIP3. Oocytes upregulate expression FUNDC1 in response diverse insults, including mtDNA mutations damage, uncoupling stress, dysfunction, thereby promoting selection against mitochondria. Loss leads increased inheritance impaired bioenergetic progeny, resulting diminished extinction descendent populations. Our findings reveal FUNDC1-mediated as mechanism preserves mother-to-offspring promotes continuity. These results may explain how mature many harboring mutant give rise healthy embryos with reduced mtDNA.

Language: Английский

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Trafficking of K63-polyubiquitin modified membrane proteins in a macroautophagy-independent pathway is linked to ATG9A

Molecular Biology of the Cell, Journal Year: 2025, Volume and Issue: 36(4)

Published: Feb. 19, 2025

Cytoplasmic K63-linked polyubiquitin signals have well-established roles in endocytosis and selective autophagy. However, how these help to direct different cargos intracellular trafficking routes is unclear. Here we report that, when the K63-polyubiquitin signal blocked by expression of a high-affinity sensor (named Vx3), many proteins originating from plasma membrane are found trapped clusters small vesicles that colocalize with ATG9A, transmembrane protein plays an essential role Importantly, whereas ATG9A required for cluster formation, other core autophagy machinery as well cargo receptors not required. Although sequestered vesicular ATG9-dependent manner, additional needed induce LC3 conjugation. Upon removal Vx3 block, K63-polyubiquitylated rapidly delivered lysosomes. These observations suggest unexpected K63-polyubiquitin–modified proteins.

Language: Английский

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Particulars of Oral Cavity

Published: Jan. 1, 2025

Abstract Oral fluids (OFs) contain a diverse array of extracellular vesicles (EVs) that hold promise as source diagnostic information. Developing EV-based diagnostics using OFs requires an understanding the physicochemical properties and heterogeneity these EVs. This review explores strategies for differentiating EVs in OFs, including differential centrifugation, density gradient novel method based on sedimentation patterns. These techniques have revealed distinct subpopulations each associated with specific biological functions potential utility. However, complexity presents challenges, comprehensive their biogenesis composition is still emerging. Future research should focus refining EV isolation methods exploring both non-EV particles OFs.

Language: Английский

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A novel RNP compartment boosts translation in growing mouse oocytes to avoid cytoplasm dilution

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Mammalian oocytes undergo a long growth phase in the ovary, during which transcriptional levels gradually decrease. Growing must therefore accumulate maternal stores and regulate their translation to achieve successful divisions early embryo development. Using immunofluorescence, mass spectrometry electron microscopy, we identified novel transient compartment, Zollo Body, late growing mouse oocytes, constituted of RNPs organelles. Morphologically, this structure resembles Balbiani body found most vertebrate species but it stains positively for nascent active phospho-mTOR. RNAseq analysis dry measurements with or without compartment further support its key role boosting translation, allowing avoid cytoplasmic dilution despite rapid size increase, ultimately ensuring developmental potential.

Language: Английский

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Endosomal-lysosomal organellar assembly (ELYSA) structures coordinate lysosomal degradation systems through mammalian oocyte-to-embryo transition

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 17, 2025

Mouse oocytes undergo drastic changes in organellar composition and their activities during maturation from the germinal vesicle (GV) to metaphase II (MII) stage. After fertilization, embryo degrades parts of maternal components via lysosomal degradation systems, including autophagy endocytosis, as zygotic gene expression begins embryogenesis. Here, we demonstrate that endosomal-lysosomal organelles form large spherical assembly structures, termed assemblies (ELYSAs), mouse oocytes. ELYSAs are observed GV oocytes, attaining sizes up 7–8 μm diameter MII comprise tubular-vesicular structures containing endosomes lysosomes along with cytosolic components. Most also positive for an regulator, LC3. These characteristics ELYSA resemble those ELVA (endolysosomal vesicular assemblies) identified independently. The signals V1-subunit vacuolar ATPase tends be detected on periphery localization increase gradually disassemble at 2-cell stage, leading further acidification organelles. findings suggest ELYSA/ELVA maintain activity a static state timely activation early development.

Language: Английский

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The Oocyte

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

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Remodeling, compartmentalization, and degradation: a trifecta for organelle quality control during gametogenesis

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102347 - 102347

Published: April 14, 2025

Language: Английский

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