Hematopoietic stem cells depend on HIM and HER.

After a series of pioneering experiments on hematopoietic stem cell (HSC) function, including early evidence of heterogeneous stem cell behavior, Jim Till, Ernest McCulloch, and Lou Simminovitch put forward a stochastic model for stem cell proliferation. In contrast to the alternative model, called the "hemopoietic-inductive microenvironment" ("HIM") in which specific microenvironments drove specific and consistent outcomes, they coined the term "hemopoiesis engendered randomly" ("HER"), in which HSCs have intrinsic differences in the cellular state that introduce a probability of potential outcomes. The HIM (extrinsic) and HER (intrinsic) discussion continues nearly 60 years later, but the metaphor also has relevance beyond cellular decision making if one considers the infrastructure and systems supporting the actual scientists who make these advances-a different kind of HER and HIM, but no less important to sort out. This article concludes with some thoughts on how we might achieve a better balance between the HIMs and HERs undertaking the research as well.