Mouse totipotent stem cells captured and maintained through spliceosomal repression

Cell, Journal Year: 2021, Volume and Issue: 184(11), P. 2843 - 2859.e20

Published: May 1, 2021

Language: Английский

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Derivation of totipotent-like stem cells with blastocyst-like structure forming potential

Cell Research, Journal Year: 2022, Volume and Issue: 32(6), P. 513 - 529

Published: May 4, 2022

Abstract It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble from embryos. Here, we report a chemical cocktail enables the derivation of totipotent-like cells, designated as potential (TPS) 2-cell mouse embryos extended pluripotent these TPS can be stably maintained long term vitro. shared features with terms totipotency markers, transcriptome, chromatin accessibility DNA methylation patterns. In vivo chimera formation assays show have embryonic extraembryonic developmental potentials at single-cell level. Moreover, induced into blastocyst-like structures resembling preimplantation blastocysts. Mechanistically, inhibition HDAC1/2 DOT1L activity activation RARγ signaling are important for inducing maintaining cells. Our study opens up new path toward fully capturing

Language: Английский

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Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Dec. 2, 2022

Abstract Pluripotent stem cells hold great promise in regenerative medicine and developmental biology studies. Mitochondrial metabolites, including tricarboxylic acid (TCA) cycle intermediates, have been reported to play critical roles pluripotency. Here we show that TCA enzymes Pdha1, Pcb, Aco2, Cs, Idh3a, Ogdh, Sdha Mdh2 are translocated the nucleus during somatic cell reprogramming, primed-to-naive transition totipotency acquisition. The nuclear-localized Idh3a promote reprogramming transition. In addition, enzymes, particularly nuclear-targeted facilitate 2-cell program pluripotent cells. Mechanistically, nuclear Pdha1 increases acetyl-CoA metabolite pool nucleus, leading chromatin remodeling at pluripotency genes by enhancing histone H3 acetylation. Our results reveal an important role of mitochondrial epigenetic regulation constitutes a mitochondria-to-nucleus retrograde signaling mode different states

Language: Английский

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DNA replication fork speed underlies cell fate changes and promotes reprogramming

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(3), P. 318 - 327

Published: March 1, 2022

Abstract Totipotency emerges in early embryogenesis, but its molecular underpinnings remain poorly characterized. In the present study, we employed DNA fiber analysis to investigate how pluripotent stem cells are reprogrammed into totipotent-like 2-cell-like (2CLCs). We show that totipotent of mouse embryo have slow replication fork speed and 2CLCs recapitulate this feature, suggesting underlies transition a state. emerge concomitant with display changes timing (RT), particularly during S-phase. RT occur prior 2CLC emergence, may predispose gene expression consequent reprogramming cell fate. Slowing down experimentally induces 2CLCs. vivo, slowing improves efficiency somatic nuclear transfer. Our data suggest regulates cellular plasticity remodeling features leads fate reprogramming.

Language: Английский

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Emerging trends in organ-on-a-chip systems for drug screening

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(6), P. 2483 - 2509

Published: Feb. 15, 2023

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially pharmaceutical industry and healthcare services. Assessment efficacy safety prior human clinical trials crucial part development, which deserves greater emphasis reduce cost time in discovery. Recent advances microfabrication tissue engineering have given rise organ-on-a-chip, an

Language: Английский

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Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(9), P. 1130 - 1147

Published: Aug. 24, 2023

Language: Английский

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Hallmarks of totipotent and pluripotent stem cell states

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(3), P. 312 - 333

Published: Feb. 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.

Language: Английский

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Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming

Cell stem cell, Journal Year: 2018, Volume and Issue: 23(1), P. 31 - 45.e7

Published: June 21, 2018

Language: Английский

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Nanocomposites Based on Biodegradable Polymers

Materials, Journal Year: 2018, Volume and Issue: 11(5), P. 795 - 795

Published: May 15, 2018

In the present review paper, our main results on nanocomposites based biodegradable polymers (on a time scale from 2010 to 2018) are reported. We mainly focused attention commercial polymers, which we mixed with different nanofillers and/or additives final aim of developing new materials tunable specific properties. A wide list have been considered according their shape, properties, and functionalization routes, discussed looking at roles basis adopted processing routes (solvent-based or melt-mixing processes). Two application fields nanocomposite considered: interaction stem cells in regenerative medicine applications as antimicrobial active role selected food packaging critically revised, providing an overview authors’ contribution state art field polymeric nanocomposites.

Language: Английский

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Argonaute Proteins: From Structure to Function in Development and Pathological Cell Fate Determination

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 7

Published: Jan. 22, 2020

The highly conserved Argonaute protein family members play a central role in the regulation of gene expression networks, orchestrating establishment and maintenance cell identity throughout entire life cycle, as well several human disorders, including cancers. Four functional proteins (AGO1-4), with high structure similarity, have been described humans mice. Interestingly, only AGO2 is robustly expressed during mouse early development, contrast to other AGOs. Consequently, indispensable for development vivo vitro. Here, we review roles by focusing on interplay between specific domains their function. Moreover, report recent works highlighting importance AGO post-translational modifications cancer.

Language: Английский

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