Partial restoration of impaired reconstitution ability of aged HSPCs and expression changes of aging-associated genes by reexpression of Utx. (A) Reexpression of Utx in aged HSPCs and the results of reconstitution. Experimental procedure (top). Aged (20 months [M]) LSKs were transduced with empty vector (EV)-, wild-type Utx (Utx^WT)-, or demethylase-dead Utx (Utx^DD)-IRES-EGFP and c-kit⁺, EGFP⁺ cells were subjected to competitive repopulation assays. The PB chimerisms of Aged+EV, Aged+Utx^WT, or Aged+Utx^DD cell transplant recipients at 3 months after transplantation (bottom left). The successfully reconstituted Aged+Utx^WT cell (Ly5.2⁺ >1.0%) transplant recipients are numbered. Correlation between relative Utx expression levels in Ly5.2⁺ BM cells and percentages of myeloid cells in Ly5.2⁺ PB cells in Aged+Utx^WT cell recipients (bottom right). The numbered mice are the same in both panels. (B) Changes in H3K27me3 expression (top; ***P < .001) and levels of selectin P (SelP) and clusterin (Clu) in Aged+EV and Aged+Utx c-kit⁺, EGFP⁺ cells (bottom). *P < .05; **P < .01.