The disproportionate expansion of telencephalic structures during human evolution involved tradeoffs that imposed greater connectivity and metabolic demands on midbrain dopaminergic neurons. Despite the central role of dopaminergic neurons in human-enriched disorders, molecular specializations associated with human-specific features and vulnerabilities of the dopaminergic system remain unexplored. Here, we establish a phylogeny-in-a-dish approach to examine gene regulatory evolution by differentiating pools of human, chimpanzee, orangutan, and macaque pluripotent stem cells into ventral midbrain organoids capable of forming long-range projections, spontaneous activity, and dopamine release.
View Article and Find Full Text PDFMammalian brains vary in size, structure, and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved. Recent studies suggest there is a primate-specific population of striatal inhibitory interneurons, the TAC3 interneurons. However, there has not yet been a detailed analysis of the spatial and phylogenetic distribution of this population.
View Article and Find Full Text PDFThe directed differentiation of pluripotent stem cells (PSCs) from panels of genetically diverse individuals is emerging as a powerful experimental system for characterizing the impact of natural genetic variation on developing cell types and tissues. Here, we establish new PSC lines and experimental approaches for modeling embryonic development in a genetically diverse, outbred mouse stock (Diversity Outbred mice). We show that a range of inbred and outbred PSC lines can be stably maintained in the primed pluripotent state (epiblast stem cells -- EpiSCs) and establish the contribution of genetic variation to phenotypic differences in gene regulation and directed differentiation.
View Article and Find Full Text PDFThis Letter reports the observation of single top quarks produced together with a photon, which directly probes the electroweak coupling of the top quark. The analysis uses 139 fb^{-1} of 13 TeV proton-proton collision data collected with the ATLAS detector at the Large Hadron Collider. Requiring a photon with transverse momentum larger than 20 GeV and within the detector acceptance, the fiducial cross section is measured to be 688±23(stat) _{-71}^{+75}(syst) fb, to be compared with the standard model prediction of 515_{-42}^{+36} fb at next-to-leading order in QCD.
View Article and Find Full Text PDFThis Letter reports the observation of τ-lepton-pair production in ultraperipheral lead-lead collisions Pb+Pb→Pb(γγ→ττ)Pb and constraints on the τ-lepton anomalous magnetic moment a_{τ}. The dataset corresponds to an integrated luminosity of 1.44 nb^{-1} of LHC Pb+Pb collisions at sqrt[s_{NN}]=5.
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