FUS expression in FUS-GFP mice increases in HSCs with aging and during serial transplantation (upper panels). FUS undergoes LLPS and forms dynamic and reversible condensates. Locally, genomic domains show strong self-interactions and are insulated from nearby regions, forming TADs. In mammals, CTCF-binding sites on chromatin are preferentially found at TAD boundaries. Inside each TAD, cohesin-mediated loop domains facilitate chromatin folding. Once cohesin is loaded onto chromatin, it moves along chromatin and presumably extrudes chromatin loops. Cohesin sliding can be blocked by CTCF, where loop boundaries form (middle panels). Aberrant phase-separated FUS limits the binding of CTCF to its motif, thereby compromising the insulation of TAD by CTCF in aged FUS^high HSCs. Consequently, the boundaries of a large number of TADs in FUS^high HSCs were merged (lower panels).