Language

English

Publication Date

4-2-2026

Journal

Biomolecules

DOI

10.3390/biom16040531

PMID

42072652

PMCID

PMC13113505

PubMedCentral® Posted Date

4-2-2026

PubMedCentral® Full Text Version

Post-print

Abstract

NANOG overexpression has been reported to reverse aging-associated decline in mesenchymal stem/stromal cell (MSC) function, but the molecular machinery engaged by NANOG in MSCs remains incompletely defined. Here, we applied APEX proximity labeling coupled with quantitative mass spectrometry to define the NANOG proximity interactome (proxeome) in human MSCs. Of 1040 quantified proteins, 828 were significantly enriched in the APEX-NANOG (H2O2 labeling) samples, consistent with a broad NANOG-centered neighborhood rather than a single stoichiometric complex. Enriched proteins encompass RNA-processing pathways (including splicing/RNP factors and selected m6A-related proteins), transcriptional coactivation and elongation control (Mediator and 7SK/P-TEFb regulators), chromatin repression/poising modules (Polycomb and HDAC/NuRD/CoREST/SIN3), ATP-dependent chromatin remodeling (BAF/SWI-SNF), three-dimensional genome organization and replication-coupled chromatin maintenance (CTCF/cohesin, CHAF1A, RIF1, UHRF1), and regulators of MSC identity and signal integration (Hippo/mechanotransduction and TGFβ-linked transcriptional circuits). Together, these data provide a spatial proteomic map of NANOG-associated nuclear neighborhoods in MSCs and a foundation for mechanistic hypotheses for how NANOG may stabilize stem-like programs.

Keywords

Humans, Mesenchymal Stem Cells, Nanog Homeobox Protein, Proteomics, Chromatin, NANOG, mesenchymal stem/stromal cells, rejuvenation, aging, APEX, proximity proteomics, RNA processing, chromatin remodeling, DNA replication, transcription elongation, mechanotransduction

Published Open-Access

yes

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