Dataset Information

Targeting PURPL RNA Enabled Rejuvenation of Senescence Cells via Epigenetic Reprogramming

ABSTRACT: Cellular senescence is a fundamental driver of ageing and age-related diseases, characterized by irreversible growth arrest and profound epigenetic alterations. While long non-coding RNAs (lncRNAs) have emerged as key regulators of senescence, their potential for senescent cell rejuvenation remains unexplored. Here, we identify the ageing-associated lncRNA PURPL as an epigenetic regulator that controls cellular rejuvenation through H3K9me3-mediated transcriptional silencing. CRISPRi-mediated PURPL depletion produces striking rejuvenation effects, resulting in restored youthful cell morphology, as well as suppression of senescence markers such as p21 and SA-β-gal. Conversely, PURPL overexpression accelerates cellular senescence, recapitulating the transcriptional and phenotypic hallmarks of ageing. Mechanistically, nuclear-localized PURPL regulates H3K9me3 deposition at 411 genomic loci including SERPINE1 (PAI-1) and EGR1, which are key senescence drivers. PURPL-mediated H3K9me3 loss at these loci derepresses their transcription, establishing a pro-senescence gene expression program. These findings reveal that PURPL is an epigenetic modulator of senescence and highlight its potential as a therapeutic target for age-related pathologies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: wenkai yi

LAB HEAD: Jian Yan

PROVIDER: PXD068664 | Pride | 2025-10-27

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 8

Publications

Targeting PURPL RNA enabled rejuvenation of senescence cells via epigenetic reprogramming.

Wang Jie J Yang Xiao X Su Xinyu X Yi Wenkai W Sun Wei W Wei Jie J Ning Yong-Qiang YQ Yan Jian J

Journal of translational medicine 20251017 1

Cellular senescence is a fundamental driver of ageing and age-related diseases, characterized by irreversible growth arrest and profound epigenetic alterations. While long non-coding RNAs (lncRNAs) have emerged as key regulators of senescence, their potential for senescent cell rejuvenation remains unexplored. Here, we identify the ageing-associated lncRNA PURPL as an epigenetic regulator that controls cellular rejuvenation through H3K9me3-mediated transcriptional silencing. CRISPRi-mediated PUR ...[more]

PMID: 41107828

Similar Datasets

Project description:Background: Vascular calcification is a ubiquitous ageing pathology markedly accelerated in patients with metabolic disorders including diabetes and renal failure. Prelamin A is a biomarker of vascular ageing which accelerates vascular smooth muscle cell (VSMC) senescence and calcification. Using prelamin A as a model we explored the earliest events in VSMC ageing, focussing on the epigenetic landscape as an environmentally modifiable target. Methods: Adenoviral expression of prelamin A was used to induce VSMC ageing and epigenetic modifications were monitored using immunofluorescence and targeted PCR-arrays. Epigenetic findings were verified in vitro using drugs targeting epigenetic modifiers and in vivo using immunohistochemistry in human vessels from young, aged and calcified patients. Transcriptomics, ChIP-seq and antibody arrays were used to identify and verify gene targets impacted by changes in the epigenetic landscape and to monitor effects on inflammation, ageing indices and calcification. A novel mouse model of VSMC-specific inducible prelamin A expression was used to study epigenetic ageing in vivo and calcification was induced with vitamin D. Results: Prelamin A accumulation in VSMCs caused rapid global alterations in the repressive heterochromatin marks, H3K9me3 and H3K27me3 which coincided with downregulation of the epigenetic writers EZH2 and SUV39H1. These same epigenetic changes were recapitulated in primary human VSMCs induced to calcify in response to mineral dysregulation and in the calcified arteries of adults, and young children on dialysis. Global analysis of H3K9me3 and H3K27me3 marks in response to prelamin A expression showed deregulation of cross-talking NF-κB and HIPK2 stress response inflammatory pathways consistent with robust activation of a senescence associated secretory phenotype (SASP). Treatment of VSMCs with EZH2 and SUV39H1 inhibitors amplified the SASP and accelerated senescence and mineral deposition. Induction of prelamin A expression in VSMCs in mice induced rapid loss of heterochromatin which preceded DNA damage and senescence and coincided with early activation of SASP factors creating an environment permissive to calcification. Conclusions: Loss of heterochromatin is accelerated by metabolic disease and acts to promote VSMC inflammaging and a tissue microenvironment prone to calcification. Pre-senescent cells with an active SASP may be an early target for tackling vascular ageing pathologies. tackling vascular ageing pathologies.

			Action	DRS
	NT1.raw	Raw
	NT2.raw	Raw
	NT3.raw	Raw
	PURPL1.raw	Raw
	PURPL2.raw	Raw