Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA; Center for Advanced Genomic Technologies, Duke University, Durham, NC 27708, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Graduate Program in Computational Biology and Bioinformatics, Duke University, Durham, NC 27708, USA; University Program in Genetics and Genomics, Duke University, Durham, NC 27708, USA; Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:
Published: December 2020
AI Article Synopsis
Article Abstract
Technologies to reprogram cell-type specification have revolutionized the fields of regenerative medicine and disease modeling. Currently, the selection of fate-determining factors for cell reprogramming applications is typically a laborious and low-throughput process. Therefore, we use high-throughput pooled CRISPR activation (CRISPRa) screens to systematically map human neuronal cell fate regulators. We utilize deactivated Cas9 (dCas9)-based gene activation to target 1,496 putative transcription factors (TFs) in the human genome. Using a reporter of neuronal commitment, we profile the neurogenic activity of these factors in human pluripotent stem cells (PSCs), leading to a curated set of pro-neuronal factors. Activation of pairs of TFs reveals neuronal cofactors, including E2F7, RUNX3, and LHX8, that improve conversion efficiency, subtype specificity, and maturation of neuronal cell types. Finally, using multiplexed gene regulation with orthogonal CRISPR systems, we demonstrate improved neuronal differentiation with concurrent activation and repression of target genes, underscoring the power of CRISPR-based gene regulation for programming complex cellular phenotypes.
Department of Human Anatomy, Co-Innovation Center of Neuroregeneration, Nantong University, No.19 Qixiu Road, Nantong, 226001, Jiangsu, People's Republic of China.
Background And Objectives: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder that mostly affects the central nervous system and skeletal muscle. This study provides a comprehensive summary of the clinical symptoms, multisystemic pathogenesis, and genetic characteristics of MELAS syndrome. The aim was to improve comprehension of clinical practice and gain a deeper understanding of the latest pathophysiological theories.
Doublecortin (DCX) is a microtubule-associated protein known to be a key regulator of neuronal migration and differentiation during brain development. However, the role of DCX, particularly in regulating the survival and growth of glioma cells, remains unclear. In this study, we utilized CRISPR/Cas9 technology to knock down DCX in the human glioma cell line (U251).
Background: Doxorubicin-induced cardiotoxicity is still an important medical problem associated with a high mortality rate in cancer survivors. p53 plays a key role in doxorubicin-induced cardiotoxicity. Diacylglycerol kinase ζ (Dgkζ), a 130-kDa enzyme abundant in cardiomyocytes, regulates the p53 protein expression level in neurons.
Department of Applied Chemistry and Life Sciences, Graduate School of Engineering, Toyohashi University of Technology, Toyohashi, Aichi 441-8580, Japan; Center for Diversity and Inclusion, Toyohashi University of Technology, Toyohashi, Aichi, 441-8580, Japan. Electronic address:
Concerns have been raised regarding acetamiprid (ACE), a neonicotinoid insecticide, due to its potential neurodevelopmental toxicity. ACE, which is structurally similar to nicotine, acts as an agonist of nicotinic acetylcholine receptors (nAChRs) and resists degradation by acetylcholinesterase. Furthermore, ACE has been reported to disrupt neuronal transmission and induce developmental neurotoxicity and ataxia in animal models.
