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Telomere shortening in hiPSCs results in neuronal and astrocyte aging

ABSTRACT: Telomere shortening in hiPSCs results in neuronal and astrocyte aging

PROVIDER: PRJNA1003810 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25583051_1.fastq.gz	Fastqsanger.gz
	SRR25583051_2.fastq.gz	Fastqsanger.gz
	SRR25583052_1.fastq.gz	Fastqsanger.gz
	SRR25583052_2.fastq.gz	Fastqsanger.gz
	SRR25583053_1.fastq.gz	Fastqsanger.gz

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Telomere shortening in hiPSCs results in neuronal and astrocyte aging

Project description:Telomerase reverse transcriptase (TERT) plays a crucial role in maintaining telomere length, which are specialised protective caps at the end of chromosomes. The lack of in vitro aging models, particularly for the central nervous system (CNS), has impeded progress in understanding aging and age-associated neurodegenerative diseases. In this study, we aimed to explore the possibility of accelerating aging in vitro using hiPSC (human induced pluripotent stem cell) technology. To achieve this, we utilised CRISPR/Cas9 to generate TERT loss-of-function hiPSCs, resulting in a loss of telomerase function and shortened telomeres. Through directed differentiation, we generated motor neurons and astrocytes to investigate whether telomere shortening could lead to age-associated phenotypes in CNS cell types.

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Telomere Shortening Impairs PGC Fate Decision

Project description:Telomere Shortening Impairs PGC Fate Decision

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Project description:Gene expression changes of UC-model organoids derive from human colon indcued by telomere enlongation was assessed by Madecassoside treatemt (telomerase activator). Gene expression changes of human colon organoids induced by telomere shortening was assessd by MST-312 treatment (telomerase inhibitor).

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Telomere Shortening Impairs PGC Fate Decision [RNA-seq]

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Telomere Shortening Impairs PGC Fate Decision [ATAC-seq]

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Telomere shortening is associated with over-expression of subtelomeric genesin thyroid tumors.

Project description:To determine whether telomere shortening in thyroid tumors delineates gene expression of subtelomeric regions, we performed RNA sequencing in a set of tumors (n = 15) and compare gene expression profiles of subtelomeric and non-subtelomeric genes between short telomere tumors and normal telomere tumors. We defined as subtelomeric genes, those located within the 5 megabase windows (Mb) adjacent to the telomeres.

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Telomeric 8-Oxoguanine Drives Rapid Premature Senescence in the Absence of Telomere Shortening

Project description:Oxidative stress is a primary cause of cellular senescence and contributes to the pathogenesis of numerous human diseases. Oxidative damage to telomeric DNA is proposed to trigger premature senescence by accelerating telomere shortening. Here we tested this model directly using a precision tool to produce the common base lesion 8-oxoguanine (8oxoG) exclusively at telomeres in human fibroblast and epithelial cells. A single induction of telomeric 8oxoG is sufficient to trigger multiple hallmarks of p53-dependent senescence. Telomeric 8oxoG activates ATM and ATR signaling, and enriches for markers of telomere dysfunction in replicating, but not quiescent cells. Acute 8oxoG production fails to shorten telomeres, but rather generates fragile sites and delayed mitotic DNA synthesis at telomeres, indicative of impaired replication. Based on our results we propose that oxidative stress promotes rapid senescence by producing oxidative base lesions which drive replication-dependent telomere fragility and dysfunction in the absence of shortening and shelterin loss.

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Telomere Shortening Impairs PGC Fate Decision [RNA-seq]

Project description:We asked whether telomere shortening impairs differentiation of ESCs into germ cell lineage. Terc-/- ESCs were used to investigate the effects of short telomeres on germ cell specification by in vitro differentiation. Short telomeres greatly reduced induction of PGCLCs from ESCs. Mechanistically, short telomeres resulted in excessive chromatin accessibility, which in turn activated the genes regulated by chromatin. Notably, Fst overexpression reduced BMP-Smad signaling and thus induction of PGCLCs, meanwhile upregulation of MAPK signaling pathway increase somatic lineage differentiation in short telomeres sampels. Moreover, knockin of Terc gene by CRISPR/Cas9 in Terc-/- ESCs restored telomere length and normal gene expression profile, and rescued PGCLC induction, revealing important roles of telomeres in PGC fate decision.

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Gene expression changes by telomere shortening in human colonic organoids

Project description:Gene expression changes by telomere shortening in human colonic organoids

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