Nr4a1/3-null HSCs have increased cell cycle with increased oxidative stress and DNA damage. (A) Ki67 and (B) BrdU incorporation (16 hours in vivo), (C) DNA content analysis after acute NR4A1/3 codepletion. (D) BrdU incorporation analysis in HSCs from wild-type CD45.1 recipient mice transplanted with 2 million CD45.2 surface marked control or CDKO bone marrow together with CD45.1 competitor at a 1:1 ratio. Daily tamoxifen treatment was initiated 6 weeks after transplant, and BrdU incorporation was analyzed 4 days after tamoxifen treatment. (E) γH2Ax in levels in LSK cells separated by cell cycle stage using 4′,6-diamidino-2-phenylindole (DAPI), (F) reactive oxidative species levels in HSCs measured by CellROX fluorescent dye, and (G) frequency of AnnexinV-positive cells in HSPCs after acute codepletion of NR4A1/3. Results expressed as mean ± SD, n = 3 to 5 mice per group. *P ≤ .05; **P ≤ .01; ***P ≤ .001.