A fly’s eye view of quiescent neural stem cells DOI Creative Commons
Mahekta R. Gujar, Hongyan Wang

Oxford Open Neuroscience, Год журнала: 2022, Номер 1

Опубликована: Янв. 1, 2022

Abstract The balance between proliferation and quiescence of stem cells is crucial in maintaining tissue homeostasis. Neural (NSCs) the brain have ability to be reactivated from a reversible quiescent state generate new neurons. However, how NSCs transit reactivation remains largely elusive. Drosophila larval NSCs, also known as neuroblasts, emerged an excellent vivo model study molecular mechanisms underlying NSC reactivation. Here, we discuss our current understanding Drosophila. We review most recent advances on epigenetic regulations microtubule cytoskeleton their cross-talk with signaling pathways that are required regulating

Язык: Английский

Trophoblast PR-SET7 dysfunction induces viral mimicry response and necroptosis associated with recurrent miscarriage DOI Creative Commons
Xiaobo Zhou, Yingchun Xu, S. Ren

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(25)

Опубликована: Июнь 12, 2023

Recurrent miscarriage (RM) is a distressing pregnancy complication. While the etiology of RM remains unclear, growing evidence has indicated relevance trophoblast impairment to pathogenesis RM. PR-SET7 sole enzyme catalyzing monomethylation H4K20 (H4K20me1) and been implicated in many pathophysiological processes. However, how functions trophoblasts its remain unknown. Here, we found that trophoblast-specific loss Pr-set7 mice led defective trophoblasts, resulting early embryonic loss. Mechanistic analysis revealed deficiency derepressed endogenous retroviruses (ERVs), leading double-stranded RNA stress subsequent viral mimicry, which drove overwhelming interferon response necroptosis. Further examination discovered H4K20me1 H4K20me3 mediated inhibition cell-intrinsic expression ERVs. Importantly, dysregulation corresponding aberrant epigenetic modifications were observed placentas Collectively, our results demonstrate acts as an transcriptional modulator essential for repressing ERVs ensuring normal fetal survival, sheds new light on potential causes contributing

Язык: Английский

Процитировано

14
Is There a Histone Code for Cellular Quiescence? DOI Creative Commons
Kenya Bonitto,

Kirthana Sarathy,

Kaiser Atai

и другие.

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

Опубликована: Окт. 29, 2021

Many of the cells in our bodies are quiescent, that is, temporarily not dividing. Under certain physiological conditions such as during tissue repair and maintenance, quiescent receive appropriate stimulus induced to enter cell cycle. The ability successfully transition into out a state is crucial for many biological processes including wound healing, stem immunological responses. Across species tissues, transcriptional, epigenetic, chromosomal changes associated with between proliferation quiescence have been analyzed, some consistent identified. Histone modifications shown play role chromatin packing accessibility, nucleosome mobility, gene expression, chromosome arrangement. In this review, we critically evaluate different histone marks these entry exit. We consider model systems quiescence, each most frequently monitored candidate marks, their writers, erasers readers. highlight data support contributing observed quiescence. specifically ask whether there “code,” mechanism whereby language encoded by specific combinations read relayed downstream modulate function. conclude highlighting emerging technologies can be applied gain greater insight code

Язык: Английский

Процитировано

24
Drosophila melanogasterSet8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation DOI Open Access
Aaron T. Crain, Megan B Butler, Christina A. Hill

и другие.

Genes & Development, Год журнала: 2024, Номер unknown

Опубликована: Июнь 12, 2024

Monomethylation of lysine 20 histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects genome function that are mediated H4K20me binding proteins. We interrogated this model a developing animal comparing parallel the transcriptomes null , K20R/A l(3)mbt mutant Drosophila melanogaster . found gene expression profiles K20A K20R larvae markedly different than despite similar reductions H4K20me1. cells have severely disrupted transcriptome fail proliferate vivo, but these phenotypes not recapitulated mutation K20 indicating developmental defects animals largely due H4K20me1-independent effects on expression. Furthermore, H4K20me1 protein L(3)mbt recruited transcription start sites most genes independently even though bound high levels Moreover, both bind purified H4K20R nucleosomes vitro. conclude changes mutants cannot be explained loss or chromatin therefore does large role

Язык: Английский

Процитировано

4
Histone lysine methyltransferase Pr‐set7/SETD8 promotes neural stem cell reactivation DOI Creative Commons
Jiawen Huang, Mahekta R. Gujar, Qiannan Deng

и другие.

EMBO Reports, Год журнала: 2021, Номер 22(4)

Опубликована: Фев. 10, 2021

The ability of neural stem cells (NSCs) to switch between quiescence and proliferation is crucial for brain development homeostasis. Increasing evidence suggests that variants histone lysine methyltransferases including KMT5A are associated with neurodevelopmental disorders. However, the function KMT5A/Pr-set7/SETD8 in central nervous system not well established. Here, we show Drosophila Pr-Set7 a novel regulator NSC reactivation. Loss pr-set7 causes delay reactivation loss H4K20 monomethylation brain. Through NSC-specific vivo profiling, demonstrate Pr-set7 binds promoter region cyclin-dependent kinase 1 (cdk1) Wnt pathway transcriptional co-activator earthbound1/jerky (ebd1). Further validation indicates required expression cdk1 ebd1 Similar Pr-set7, Cdk1 Ebd1 promote Finally, overexpression significantly suppressed defects observed pr-set7-depleted brains. Therefore, promotes by regulating signaling cell cycle progression. Our findings may contribute understanding mammalian KMT5A/PR-SET7/SETD8 during development.

Язык: Английский

Процитировано

21
Epigenetic regulation of neural stem cell aging in the mouse hippocampus by Setd8 downregulation DOI Creative Commons

Shuzo Matsubara,

Kanae Matsuda‐Ito,

Haruka Sekiryu

и другие.

The EMBO Journal, Год журнала: 2025, Номер unknown

Опубликована: Июнь 3, 2025

Neural stem cells (NSCs) in the mammalian brain decline rapidly with age, leading to impairment of hippocampal memory function later life. However, relationship between epigenetic remodeling and transcriptional regulation that compromises NSC activity during early stage chronological aging remains unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) ATAC (scATAC-seq) on NSCs newly generated neurons across different stages. Integrated data analysis revealed continuous alterations chromatin profile their progeny from neonatal mature adult stages, accompanied by consistent changes profiles. Further, decreased expression Setd8, encoding enzyme for histone H4 monomethylation at lysine 20 (H4K20me1), underlies age-related mouse NSCs. Notably, depletion Setd8 elicits gene phenocopy changes, impairs activity, deficits. Together, our study provides a global map longitudinal transcriptome identifies mechanistic insights into early-onset neurogenesis precedes functional aging.

Язык: Английский

Процитировано

0
Astrocytes control quiescent NSC reactivation via GPCR signaling–mediated F-actin remodeling DOI Creative Commons
Kun‐Yang Lin, Mahekta R. Gujar, Jiaen Lin

и другие.

Science Advances, Год журнала: 2024, Номер 10(30)

Опубликована: Июль 24, 2024

The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development homeostasis. Defects in NSC reactivation are associated with neurodevelopmental disorders.

Язык: Английский

Процитировано

3
Drosophila melanogasterSet8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation DOI Creative Commons
Aaron T. Crain, Megan B Butler, Christina A. Hill

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 18, 2024

Abstract Mono-methylation of Lysine 20 histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects genome function that are mediated H4K20me-binding proteins. We interrogated this model a developing animal comparing parallel the transcriptomes null , K20R/A l(3)mbt mutant Drosophila melanogaster . found gene expression profiles K20A K20R larvae markedly different than despite similar reductions H4K20me1. cells have severely disrupted transcriptome fail proliferate vivo but these phenotypes not recapitulated mutation K20 indicating developmental defects animals largely due H4K20me1-independent effects on expression. Further, H4K20me1 binding protein L(3)mbt recruited transcription start sites most genes independently H4K20me even though bound high levels Moreover, both bind purified H4K20R nucleosomes vitro. conclude changes mutants cannot be explained loss or chromatin, therefore does large role

Язык: Английский

Процитировано

2
Quiescent Adult Neural Stem Cells: Developmental Origin and Regulatory Mechanisms DOI Creative Commons
Meng Han, Huan Yu, Kun Zhang

и другие.

Neuroscience Bulletin, Год журнала: 2024, Номер 40(9), С. 1353 - 1363

Опубликована: Апрель 24, 2024

The existence of neural stem cells (NSCs) in the adult mammalian nervous system, although small number and restricted to sub-ventricular zone lateral ventricles, dentate gyrus hippocampus, olfactory epithelium, is a gift evolution for adaptive brain function which requires persistent plastic changes these regions. It known that most NSCs are latent, showing long cell cycles. In past decade, concept quiescent (qNSCs) has been widely accepted by researchers field, great progress made biology qNSCs. Although spontaneous neuronal regeneration derived from not significant, understanding how behaviors qNSCs regulated sheds light on stimulating endogenous NSC-based regeneration. this review, we mainly focus recent developmental origin regulatory mechanisms maintain under normal conditions, mobilize pathological hoping give some insights future study.

Язык: Английский

Процитировано

2
H4K20me1 plays a dual role in transcriptional regulation of regeneration and axis patterning inHydra DOI Creative Commons
Akhila Gungi, Shagnik Saha, Mrinmoy Pal

и другие.

Life Science Alliance, Год журнала: 2023, Номер 6(5), С. e202201619 - e202201619

Опубликована: Март 21, 2023

The evolution of the first body axis in animal kingdom and its extensive ability to regenerate makes Hydra , a Cnidarian, an excellent model system for understanding underlying epigenetic mechanisms. We identify that monomethyltransferase SETD8 is critical regeneration because conserved interaction with β-catenin fine-tune associated gene regulatory network. Inhibition activity abolishes head foot . Furthermore, we show H4K20me1, histone mark imparted by SETD8, colocalizes transcriptional activation machinery locally at β-catenin-bound TCF/LEF-binding sites on promoters head-associated genes, marking mode. In contrast, genome-wide analysis H4K20me1 occupancy revealed negative correlation activation. propose acts as general repressive Cnidaria describe dichotomous role regulation

Язык: Английский

Процитировано

5
Promoting Endogenous Neurogenesis as a Treatment for Alzheimer’s Disease DOI
Qiang Zhang, Jingyue Liu, Li Chen

и другие.

Molecular Neurobiology, Год журнала: 2022, Номер 60(3), С. 1353 - 1368

Опубликована: Ноя. 29, 2022

Язык: Английский

Процитировано

8