ZKSCAN3 counteracts cellular senescence by stabilizing heterochromatin

Nucleic Acids Research, Год журнала: 2020, Номер 48(11), С. 6001 - 6018

Опубликована: Май 8, 2020

Abstract Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) has long been known as a master transcriptional repressor of autophagy. Here, we identify novel role for ZKSCAN3 in alleviating senescence that is independent its autophagy-related activity. Downregulation observed aged human mesenchymal stem cells (hMSCs) depletion accelerates these cells. Mechanistically, maintains heterochromatin stability via interaction heterochromatin-associated proteins nuclear lamina proteins. Further study shows deficiency results the detachment genomic lamina-associated (LADs) from lamina, loss heterochromatin, more accessible chromatin status consequently, aberrant transcription repetitive sequences. Overexpression not only rescues premature phenotypes ZKSCAN3-deficient hMSCs but also rejuvenates physiologically pathologically senescent hMSCs. Together, data reveal first time functions an epigenetic modulator to maintain organization thereby attenuate cellular senescence. Our findings establish new functional link among ZKSCAN3, regulation, cell aging.

Язык: Английский

---

Large-scale chromatin reorganization reactivates placenta-specific genes that drive cellular aging

Developmental Cell, Год журнала: 2022, Номер 57(11), С. 1347 - 1368.e12

Опубликована: Май 24, 2022

Язык: Английский

---

The Mechanism of Stem Cell Aging

Stem Cell Reviews and Reports, Год журнала: 2022, Номер 18(4), С. 1281 - 1293

Опубликована: Янв. 9, 2022

Abstract Stem cells have self-renewal ability and multi-directional differentiation potential. They tissue repair capabilities are essential for maintaining the homeostasis. The depletion of stem is closely related to occurrence body aging aging-related diseases. Therefore, revealing molecular mechanisms cell will set new directions therapeutic application cells, study mechanisms, prevention treatment This review comprehensively describes provides basis further investigations aimed at developing anti-stem strategies promoting clinical cells.

Язык: Английский

---

Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging

Cell Reports, Год журнала: 2023, Номер 42(6), С. 112593 - 112593

Опубликована: Май 31, 2023

The primate frontal lobe (FL) is sensitive to aging-related neurocognitive decline. However, the aging-associated molecular mechanisms remain unclear. Here, using physiologically aged non-human primates (NHPs), we depicted a comprehensive landscape of FL aging with multidimensional profiling encompassing bulk and single-nucleus transcriptomes, quantitative proteome, DNA methylome. Conjoint analysis across these neuropathological layers underscores nuclear lamina heterochromatin erosion, resurrection endogenous retroviruses (ERVs), activated pro-inflammatory cyclic GMP-AMP synthase (cGAS) signaling, cellular senescence in post-mitotic neurons NHP human FL. Using embryonic stem-cell-derived recapitulating vitro, verified loss B-type lamins inducing ERVs as an initiating event aging-bound cascade neurons. Of significance, changes can be alleviated by abacavir, nucleoside reverse transcriptase inhibitor, either through direct treatment senescent vitro or oral administration mice.

Язык: Английский

---

Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation

Cell stem cell, Год журнала: 2023, Номер 30(11), С. 1452 - 1471.e10

Опубликована: Окт. 12, 2023

Язык: Английский

---