SUMMARY Stem-cell differentiation to desired lineages requires navigating alternating developmental paths often leading to unwanted cell-types. Hence comprehensive developmental roadmaps are crucial to channel stem-cell differentiation towards desired fates. To this end, here we map bifurcating lineage choices leading from pluripotency to twelve human mesodermal lineages, including bone, muscle and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation towards unwanted fates and rapidly steer pluripotent stem cells towards 80–99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously-unobservable human embryonic event transiently marked by HOPX expression. Collectively this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes.

Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1+ PD-L1+ myeloid cells. In a further transcriptomic meta-analysis of peripheral blood from patients with TB, immunoregulatory trends mirror those identified by granuloma imaging. Notably, PD-L1 expression is associated with progression to active TB and treatment response. These data indicate that in TB granulomas, there are local spatially coordinated immunoregulatory programs with systemic manifestations that define active TB.

BaTiO 3 / SrTiO 3 superlattices are found to have a critical periodicity of 30 SrTiO3 unit cells, below which the room-temperature symmetry is mm2 orthorhombic. The orthorhombic-tetragonal phase-transition temperature is shifted upward from the bulk value (<3 K and normally not observed at finite temperature) of the quantum paraelectric pure strontium titanate to temperatures above ambient (599 K for 30/30-unit-cell superlattices). Antidipole patterns appear in superlattices with unit cells below 10/10. A model is presented that accounts quantitatively for the change in second-harmonic generation intensity with superlattice periodicity from 4 unit cells to 50.

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