HSC viability, mitogenesis and self-maintenance can be separately regulated by different external cues. (A) Schema showing the multiple responses that can affect HSC numbers. (B) Demonstration that different extrinsic conditions can separately regulate the survival, proliferation, and self-renewal responses of highly purified, durable LTRCs assessed in single-cell cultures. Shown are examples of different in vitro conditions in which full LTRC activity of the surviving input cells was maintained for 7 days either in the absence of cell death or division, or under different conditions that variably kept the input cells alive but maximally stimulated mitogenesis of the survivors. Also shown are conditions that supported full survival and mitogenesis of the same input cells, but with substantial loss of their original LTRC activity (redrawn from data published in Wohrer et al⁶⁵  with permission). ESLAM, EPCR⁺CD48⁻CD150⁺; FBS, fetal bovine serum; EP, erythropoietin; SF, Steel factor; CM, UG26 stromal cell conditioned medium; LDA, limiting dilution assay.