Functional Maturation of hPSC-Derived Forebrain Interneurons Requires an Extended Timeline and Mimics Human Neural Development Researchers report the directed differentiation of human pluripotent stem cells (hPSCs) into medial ganglionic eminence-like progenitors and their maturation into forebrain type interneurons. They found that early-stage progenitors progress via a radial glial-like stem cell enriched in the human fetal brain. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release Directed Differentiation and Functional Maturation of Cortical Interneurons from Human Embryonic Stem Cells Investigators demonstrated the highly efficient derivation of human cortical interneurons in an NKX2.1::GFP human embryonic stem cell reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neurotransmitter phenotypes, and migratory behaviors. [Cell Stem Cell] Abstract | Graphical Abstract Expansion of Oligodendrocyte Progenitor Cells following SIRT1 Inactivation in the Adult Brain Scientists showed that genetic inactivation of SIRT1, a protein deacetylase implicated in energy metabolism, increases the production of new oligodendrocyte progenitor cells (OPCs) in the adult mouse brain, in part by acting in neural stem cells. New OPCs produced following SIRT1 inactivation differentiate normally, generating fully myelinating oligodendrocytes. [Nat Cell Biol] Abstract GABA Progenitors Grafted into the Adult Epileptic Brain Control Seizures and Abnormal Behavior Scientists report that in the recipient brain, GABA progenitors migrated up to 1,500 μm from the injection site, expressed genes and proteins characteristic for interneurons, differentiated into functional inhibitory neurons and received excitatory synaptic input. [Nat Neurosci] Abstract | Press Release The Ventral Hippocampus Is the Embryonic Origin for Adult Neural Stem Cells in the Dentate Gyrus Investigators showed that the neural stem cells (NSCs) initially originate from the ventral hippocampus during late gestation and then relocate into the dorsal hippocampus. The descendants of these cells are the source for the long lived-NSCs in the subgranular zone. [Neuron] Abstract Parkin Overexpression during Aging Reduces Proteotoxicity, Alters Mitochondrial Dynamics, and Extends Lifespan Investigators showed that ubiquitous or neuron-specific up-regulation of Parkin, in adult Drosophila melanogaster, increases both mean and maximum lifespan without reducing reproductive output, physical activity, or food intake. Long-lived Parkin-overexpressing flies display an increase in K48-linked polyubiquitin and reduced levels of protein aggregation during aging. [Proc Natl Acad Sci USA] Abstract | Press Release Role for the Kinase SGK1 in Stress, Depression, and Glucocorticoid Effects on Hippocampal Neurogenesis Scientists identified the glucocorticoid receptor target gene, serum- and glucocorticoid-inducible kinase 1 (SGK1), as one such mechanism. Using a human hippocampal progenitor cell line, they found that a small molecule inhibitor for SGK1, GSK650394, counteracted the cortisol-induced reduction in neurogenesis. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release Proteolysis of MOB1 by the Ubiquitin Ligase praja2 Attenuates Hippo Signaling and Supports Glioblastoma Growth Scientists report that the RING ligase praja2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo cascade. Degradation of Mob through the ubiquitin-proteasome system attenuates the Hippo cascade and sustains glioblastoma growth in vivo. [Nat Commun] Full Article SMRT Compounds Abrogate Cellular Phenotypes of Ataxia Telangiectasia in Neural Derivatives of Patient-Specific hiPSCs The authors present a model of human ataxia telangiectasia using induced pluripotent stem cells, and show that small molecule read-through compounds, designed to induce read-through of mRNA around premature termination codons, restore ATM activity and improve the response to DNA damage. [Nat Commun] Abstract Integrin α3 Is Overexpressed in Glioma Stem-Like Cells and Promotes Invasion Researchers attempted to identify the molecules that promote invasion in glioma stem-like cells. Immunohistochemistry demonstrated the localization of integrin α3 in glioblastoma cells, including invading cells, and in the tumor cells around the vessels, which is believed to be a stem cell niche. [Brit J Cancer] Abstract SNARE Proteins Synaptobrevin, SNAP-25, and Syntaxin Are Involved in Rapid and Slow Endocytosis at Synapses Scientists report that cleavage of three SNARE proteins essential for exocytosis, including synaptobrevin, SNAP-25, and syntaxin, inhibited rapid endocytosis at the calyx of Held nerve terminal, suggesting the involvement of the three SNARE proteins in rapid endocytosis. These SNARE proteins were also involved in slow endocytosis. [Cell Rep] Abstract | Graphical Abstract | Press Release |