PXD059860

PXD059860 is an original dataset announced via ProteomeXchange.

Title	NEAT1 Regulates BMSCs Aging Through Disruption of FGF2 Nuclear Transport
Description	Background: The aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims to elucidate how NEAT1 regulates mitotic proteins during BMSCs aging. Methods: BMSCs were isolated from alveolar bone of human volunteers aged 26–33 (young) and 66–78 (aged). NEAT1 expression and distribution changes during aging process were observed using fluorescence in situ hybridization (FISH) in young (3 months) and aged (18 months) mice or human BMSCs. Subsequent RNA pulldown and proteomic analyses, along with single-cell analysis, immunofluorescence, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP), were conducted to investigate that NEAT1 impairs the nuclear transport of mitotic FGF2 and contributes to BMSCs aging. Results: We reveal that NEAT1 undergoes significant upregulated and shifts from nucleus to cytoplasm in bone marrow and BMSCs during aging process. In which, the expression correlates with nuclear DNA content during karyokinesis, suggesting a link to mitogenic factor. Within NEAT1 knockdown, hallmarks of cellular aging, including senescence-associated secretory phenotype (SASP), p16, and p21, were significantly downregulated. RNA pulldown and proteomic analyses further identify NEAT1 involved in osteoblast differentiation, mitotic cell cycle, and ribosome biogenesis, highlighting its role in maintaining BMSCs differentiation and proliferation. Notably, as an essential growth factor of BMSCs, Fibroblast Growth Factor 2 (FGF2) directly abundant binds to NEAT1 and the sites enriched with nuclear localization motifs. Importantly, NEAT1 decreased the interaction between FGF2 and Karyopherin Subunit Beta 1 (KPNB1), influencing the nuclear transport of mitogenic FGF2. Conclusions: Our findings position NEAT1 as a critical regulator of mitogenic protein networks that govern BMSC aging. Targeting NEAT1 might offer novel therapeutic strategies to rejuvenate aged BMSCs.
HostingRepository	iProX
AnnounceDate	2025-01-16
AnnouncementXML	Submission_2025-04-24_19:09:10.266.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hengguo Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-15 23:14:28	ID requested
1	2025-03-02 18:51:10	announced
⏵ 2	2025-04-24 19:09:11	announced	2025-04-25: Add info.

Wang Z, Zhen W, Wang Q, Sun Y, Jin S, Yu S, Wu X, Zhang W, Zhang Y, Xu F, Wang R, Xie Y, Sun W, Xu J, Zhang H, NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport. Stem Cell Res Ther, 16(1):30(2025) [pubmed]

submitter keyword: BMSCs, Aging, NEAT1, FGF2, Nuclear Transport

Hengguo Zhang
contact affiliation	Anhui Medical University
contact email	zhanghengguo@ahmu.edu.cn
lab head
Hengguo Zhang
contact affiliation	Anhui Medical University
contact email	zhanghengguo@ahmu.edu.cn
dataset submitter

iProX dataset URI