Investigators reveal a hierarchical mechanism in the direct conversion of fibroblasts into induced neuronal cells mediated by the transcription factors Ascl1, Brn2, and Myt1l. [Cell] Abstract | Graphical Abstract Enhancer of Zeste Homolog 2-Mediated H3K27 Trimethylation Mediates Neurodegeneration in Ataxia-Telangiectasia
The symptoms of ataxia-telangiectasia (A-T) include a progressive neurodegeneration caused by ATM protein deficiency. The authors previously found that nuclear accumulation of histone deacetylase-4, HDAC4, contributes to this degeneration; they now report that increased trimethylation of histone H3 on Lys27 (H3K27me3) mediated by polycomb repressive complex 2 is also important in the A-T phenotype. [Nat Neurosci] Abstract | Press Release
Conserved miR-8/miR-200 Defines a Glial Niche that Controls Neuroepithelial Expansion and Neuroblast Transition
Researchers showed that loss of the Drosophila microRNA mir-8 results in both excess proliferation and ectopic neuroblast transition. Unexpectedly, mir-8 is expressed in a subpopulation of optic-lobe-associated cortex glia that extend processes that ensheath the neuroepithelium, suggesting that glia cells communicate with the neuroepithelium. [Dev Cell] Abstract
Targeting RNA Foci in iPSC-Derived Motor Neurons from ALS Patients with a C9ORF72 Repeat Expansion
Researchers report a cellular model of the familial form of amyotrophic lateral sclerosis (C9-ALS) with motor neurons differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying the C9ORF72 repeat expansion. No significant loss of C9ORF72 expression was observed, and knockdown of the transcript was not toxic to cultured human motor neurons. [Sci Transl Med] Abstract | Press Release
iPSC-Derived Neural Precursors Exert a Neuroprotective Role in Immune-Mediated Demyelination via the Secretion of LIF
Scientists showed that mouse induced pluripotent stem cells (iPSC) – derived neural stem/precursor cells – when intrathecally transplanted after disease onset-ameliorate clinical and pathological features of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. [Nat Commun] Abstract
Catecholamine Metabolism Drives Generation of Mitochondrial DNA Deletions in Dopaminergic Neurons
Scientists developed novel polymerase chain reaction strategies to detect distinct mitochondrial DNA deletions and monitor their accumulation patterns. Applying these approaches in in vitro and in vivo models, they showed that catecholamine metabolism drives the generation and accumulation of these mitochondrial DNA mutations. [Brain ] Abstract
Human Induced Pluripotent Stem Cell-Derived Cortical Neurons Integrate in Stroke-Injured Cortex and Improve Functional Recovery
Researchers generated progenitors in vitro, expressing specific cortical markers and giving rise to functional neurons, from long-term self-renewing neuroepithelial-like stem cells, produced from adult human fibroblast-derived induced pluripotent stem cells. [Brain] Abstract | Press Release
ß-Arrestin Protects Neurons by Mediating Endogenous Opioid Arrest of Inflammatory Microglia
Scientists showed that microglial ß-arrestin mediates the ability of dynorphin/kappa-opioid receptor to limit endotoxin-elicited production of pro-inflammatory effectors and cytokines, subsequently protecting neurons from inflammation-induced neurotoxicity. [Cell Death Differ] Abstract
Generation of Neuronal Progenitor Cells in Response to Tumors in the Human Brain
Scientists analyzed the tumor-parenchyma interface of neurosurgical resections for the presence of neuronal progenitor cells (NPCs) and distinguished these physiological cells from the tumor mass. They observed that PSA-NCAM-positive NPCs accumulate at the border of high-grade astrocytomas and display a marker profile consistent with immature migratory neuronal progenitor cells. [Stem Cells ] Abstract
Pten Loss in Olig2 Expressing Neural Progenitor Cells and Oligodendrocytes Leads to Interneuron Dysplasia and Leukodystrophy
Opposition of the pathway by treatment of human primary neural progenitor cells (NPCs) with the PI3K inhibitor, NVP-BKM120, blocked in vitro differentiation of neurons and oligodendroglia indicating PI3K/PTEN effects on NPCs can be bi-directional. [Stem Cells] Abstract
Protein Phosphatase 4 and Smek Complex Negatively Regulate Par3 and Promote Neuronal Differentiation of Neural Stem/Progenitor Cells
Scientists showed that Smek1, a regulatory subunit of the serine/threonine protein phosphatase PP4, promotes neuronal differentiation and suppresses the proliferative capacity of neural progenitor cells. [Cell Rep] Full Article | Graphical Abstract | Press Release