(A) Schematic diagram of a double transgenic system in which cells are labeled by controllable incorporation of a histone H2B-GFP fusion protein into chromatin. H2B-GFP is expressed via a tetracycline response element–containing promoter (TRE), which is activated by the tetracycline transactivator (tTA) driven by human CD34 promoter. Administration of doxycycline (Dox) shuts off production of the H2B-GFP transgene. (B) Quiescent nondividing cells retain GFP label, while dividing cells progressively dilute their GFP label by one-half with each cell division. (C) Histogram displaying the H2B-GFP peaks 0-4 visible within the label retaining stem cell compartment of young (3-4 months on dox) and aging mice (14-22 months on dox). Panels A and B reprinted by permission from John Wiley & Sons, Ltd: Annals of the New York Academy of Sciences doi:10.1111/j.1749-6632.2009.04608.x, copyright 2009. Panel C reprinted from Cell , Vol 167, Bernitz et al, "Hematopoietic Stem Cells Count and Remember Self-Renewal Divisions," Pages 1296-1309, Copyright 2016, with permission from Elsevier.