Vukovic et al. report that Hif-1α and Hif-2α are not required for leukemia stem cell maintenance and AML propagation, but they act synergistically to suppress leukemia development in mice. Furthermore, knockout of HIF-2α or pharmacological inhibition of the HIF pathway in human AML cells has no impact on their survival and proliferation under hypoxic conditions.

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The development of natural tissues, organs and bodies depends on mechanisms of patterning and of morphogenesis, typically (but not invariably) in that order, and often several times at different final scales. Using synthetic biology to engineer patterning and morphogenesis will both enhance our basic understanding of how development works, and provide important technologies for advanced tissue engineering. Focusing on mammalian systems built to date, this review describes patterning systems, both contact-mediated and reaction-diffusion, and morphogenetic effectors. It also describes early attempts to connect the two to create self-organizing physical form. The review goes on to consider how these self-organized systems might be modified to increase the complexity and scale of the order they produce, and outlines some possible directions for future research and development.

Branching morphogenesis of epithelia involves division of cells into leader (tip) and follower (stalk) cells. Published work on cell lines in culture has suggested that symmetry‐breaking takes place via a secreted autocrine inhibitor of motility, the inhibitor accumulating more in concave regions of the culture boundary, slowing advance of cells there, and less in convex areas, allowing advance and a further exaggeration of the concave/convex difference. Here we test this hypothesis using a two‐dimensional culture system that includes strong flow conditions to remove accumulating diffusible secretions. We find that, while motility does indeed follow boundary curvature in this system, flow makes no difference: this challenges the hypothesis of control by a diffusible secreted autocrine inhibitor.