Accession PRJCA003860
Title Nuclear SIRT3 counteracts human stem cell senescence
Relevance Medical
Data types Whole genome sequencing
Epigenomics
Raw sequence reads
Genome sequencing
Organisms Homo sapiens
Description Sirtuin 3 (SIRT3) is an NAD+-dependent deacetylase involved in various physiological and pathological processes. However, the role of SIRT3 in regulating human stem cell senescence remains largely unknown. Here, we observed the downregulated expression of SIRT3 in senescent human mesenchymal stem cells (hMSCs). SIRT3 deficiency accelerated cellular senescence in hMSCs, along with compromised nuclear integrity, loss of heterochromatin and increased DNA damage. These aging-associated nuclear defects were attenuated by the reintroduction of SIRT3. Mechanistic studies demonstrated the interaction of SIRT3 with nuclear envelope proteins and heterochromatin-associated proteins. Further findings revealed that SIRT3 deficiency led to the loss of lamina-associated domains (LADs) from the nuclear lamina, increased chromatin accessibility and aberrant transcription of repetitive sequences. Meanwhile, the overexpression of nuclear-localized SIRT3 rescued the senescence phenotypes. Taken together, our study reveals a novel role of nuclear SIRT3 in stabilizing heterochromatin and counteracting hMSC senescence, which may provide new clinical therapeutic targets to ameliorate aging-related diseases.
Sample scope Monoisolate
Release date 2020-11-13
Publication
PubMed ID Article title Journal name DOI Year
33706382 SIRT3 consolidates heterochromatin and counteracts senescence Nucleic Acids Research 10.1093/nar/gkab161 2021
Grants
Agency program Grant ID Grant title
Chinese Academy of Sciences (CAS) National Key Research and Development Program of China 2018YFC2000100
Submitter Guanghui    Liu  (ghliu@ioz.ac.cn)
Organization Institute of Zoology, Chinese Academy of Sciences
Submission date 2020-11-13

Project Data

Resource name Description
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