Nuclear FGF2 orchestrates phase separation-mediated rDNA chromatin architecture to control BMSCs cell fate.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40993129.
- Also identified by DOI 10.1038/s41413-025-00451-y and PMC identifier 12460815.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Ribosomal RNA (rRNA) synthesis is intricately tied to cellular growth and proliferation. Basic fibroblast growth factor (FGF2), a pivotal factor for bone marrow mesenchymal stem cells (BMSCs), can stimulates rRNA transcription, though the underlying mechanism remains unknown. Here, we demonstrate that the cytoplasm-nucleus translocation of FGF2 is determined by the stable nuclear localization motif. Meanwhile, the nuclear FGF2 regulates rRNA expression and BMSCs proliferation via phase separation. Next, through FGF2 related epigenomics and 3D genomes analysis, we identified chromatin architectures during BMSCs differentiation and aging. In the process, topologically associating domains (TADs) and chromatin loops profiling revealed the attenuated genomic interaction among proximal chromosomes 13, 14, 15, 21, and 22, where phase-separated FGF2 facilitates rDNA transcription depend on specific super-enhancers (SEs). Furthermore, we validated that FGF2 orchestrates rDNA chromatin architecture in coordination with STAT5. Together, these findings underscore the pivotal role of FGF2 in rDNA chromatin architectures, which determines BMSCs cell fate.
Medical subject headings
- Mesenchymal Stem Cells
- Fibroblast Growth Factor 2
- Chromatin
- DNA, Ribosomal
- Cell Nucleus