PXD051832-1

PXD051832 is an original dataset announced via ProteomeXchange.

Title	Age-associated adipose-derived stem cell activity is dictated by IGF2BP3-dependent regulation of glutamine and BCAA catabolism
Description	Aging-related diseases were commonly considered being attribute to age-dependent loss in numbers or differentiation potential, whereas aging effects on stem cell characteristics were poorly concerned. In the present study, we investigated age-related alterations of human adipose-derived stem cells (hASCs) from infant (I-hASCs) and elderly (E-hASCs) donors. Based on the integration of multi-omics analyses including scRNA-seq, proteomic, and metabolomic profiles, we unveiled the ACTA2+TAGLN+ cluster primarily confers hASC stemness and tissue repair function. In particular, E-hASCs exhibited attenuated BCAA and glutamine catabolism, potentially due to the decreased BCAT1 and GLS expression in ACTA2+TAGLN+ cluster, which subsequently reduced the energy production and ROS elimination ability of hASCs. Mechanistic studies revealed that BCAT1 and GLS were positively regulated by IGF2BP3 which was diminished in the ACTA2+TAGLN+ cluster of E-hASCs. Suppression of IGF2BP3 decreased I-hASCs self-renewal and multidirectional differentiation potential through the negative regulation of redox homeostasis and energy production, whereas BCAT1 or GLS expression can partly reverse the negative effect of IGF2BP3 knockdown. Furthermore, m6A modification of BCAT1 or GLS mRNAs is required for IGF2BP3-mediated mRNA stability, as demonstrated by the use of METTL3 shRNA or m6A inhibitors. Glutamine and BCAA supplementation effectively restored E-hASC self-renewal and multidirectional differentiation potential both in vitro and in vivo, suggesting the clinical application value to E-hASCs therapy in the treatment of aging-related diseases or in the wound healing for elder.
HostingRepository	iProX
AnnounceDate	2024-04-29
AnnouncementXML	Submission_2025-04-28_17:40:41.705.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mo He
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-29 00:25:06	ID requested
⏵ 1	2025-04-28 17:40:42	announced

Dataset with its publication pending

submitter keyword: Aging-related diseases, stem cell, proteomic, metabolomic

Mo He
contact affiliation	Nanning Monitorhelix Protein Techology
contact email	1156256010@qq.com
lab head
Mo He
contact affiliation	Nanning Monitorhelix Protein Techology
contact email	1156256010@qq.com
dataset submitter

iProX dataset URI