Different HSCs may have different requirements for survival/self-renewal. Top: All HSCs in a culture experience the same stimuli. These may expand a subset of HSCs (blue), leave another subset untouched (green), but could be detrimental for other (purple, orange) HSCs. The outcome is a modest expansion of a subset of HSCs. Bottom: In vivo, HSCs reside in niches that might provide selective stimuli to different HSC subsets. This leads to optimal self-renewal conditions for each subset of HSCs. Ex vivo HSC expansion could depend on finding distinct conditions for different HSC subsets.