Nuclear FGF2 orchestrates phase separation-mediated rDNA chromatin architecture to control BMSCs cell fate.

Hengguo Zhang, Zifei Wang, Zhenqing Liu, Xuan Li, Wansu Sun, Wenyu Zhen, Fei Xu, Rui Wang, Qi Yin, Shuqin Cao, Mingyue Wu, Jiacai He, Jianguang Xu, Yang Li, Quan Yuan

College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, China.College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, China. · pubmed

Paper

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.

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Research summary

Nuclear FGF2 regulates rRNA expression and BMSCs proliferation through phase separation, influencing chromatin architecture and cell fate. The study addresses mechanisms that could impact stem cell behavior and aging, linking FGF2 to cellular processes relevant to longevity.

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