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 transcripti...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.展开更多
基金the open research project of State Key Laboratory of Oral Diseases(no.SKLOD2024OF03)the Key Project of Natural Science Research in Anhui Provincial Universities(no.2024AH050683)+1 种基金Anhui Province Outstanding Young Teachers Development Program(no.YQYB2024013)the National Natural Science Foundation of China(no.82201026,82125006).
文摘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.
