A repository of Ogden syndrome patient derived iPSC lines and isogenic pairs by X-chromosome screening and genome-editing.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting 80% of cytosolic proteins in humans. The human essential gene, encodes the enzyme NAA10, as the catalytic subunit for the N-terminal acetyltransferase A (NatA) complex, including the accessory protein, NAA15. The first human disease directly involving was discovered in 2011, and it was named Ogden syndrome (OS), after the location of the first affected family residing in Ogden, Utah, USA.

Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS), resulting in neurological disability that worsens over time. While progress has been made in defining the immune system's role in MS pathophysiology, the contribution of intrinsic CNS cell dysfunction remains unclear. Here, we generated a collection of induced pluripotent stem cell (iPSC) lines from people with MS spanning diverse clinical subtypes and differentiated them into glia-enriched cultures.

Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis.

Multiple sclerosis (MS) is considered an inflammatory and neurodegenerative disease of the central nervous system, typically resulting in significant neurological disability that worsens over time. While considerable progress has been made in defining the immune system's role in MS pathophysiology, the contribution of intrinsic CNS-cell dysfunction remains unclear. Here, we generated the largest reported collection of iPSC lines from people with MS spanning diverse clinical subtypes and differentiated them into glia-enriched cultures.

The chemokine-like Orion bridges phosphatidylserine and Draper in phagocytosis of neurons.

Phagocytic clearance of degenerating neurons is triggered by "eat-me" signals exposed on the neuronal surface. The conserved neuronal eat-me signal phosphatidylserine (PS) and the engulfment receptor Draper (Drpr) mediate phagocytosis of degenerating neurons in . However, how PS is recognized by Drpr-expressing phagocytes in vivo remains poorly understood.

Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models.

Astrocytes respond to injury, infection, and inflammation in the central nervous system by acquiring reactive states in which they may become dysfunctional and contribute to disease pathology. A sub-state of reactive astrocytes induced by proinflammatory factors TNF, IL-1α, and C1q ("TIC") has been implicated in many neurodegenerative diseases as a source of neurotoxicity. Here, we used an established human induced pluripotent stem cell (hiPSC) model to investigate the surface marker profile and proteome of TIC-induced reactive astrocytes.

Phagocytosis and self-destruction break down dendrites of sensory neurons at distinct steps of Wallerian degeneration.

After injury, severed dendrites and axons expose the "eat-me" signal phosphatidylserine (PS) on their surface while they break down. The degeneration of injured axons is controlled by a conserved Wallerian degeneration (WD) pathway, which is thought to activate neurite self-destruction through Sarm-mediated nicotinamide adenine dinucleotide (NAD) depletion. While neurite PS exposure is known to be affected by genetic manipulations of NAD, how the WD pathway coordinates both neurite PS exposure and self-destruction and whether PS-induced phagocytosis contributes to neurite breakdown in vivo remain unknown.

Die in pieces: How Drosophila sheds light on neurite degeneration and clearance.

Dendrites and axons are delicate neuronal membrane extensions that undergo degeneration after physical injuries. In neurodegenerative diseases, they often degenerate prior to neuronal death. Understanding the mechanisms of neurite degeneration has been an intense focus of neurobiology research in the last two decades.

Robust CRISPR/Cas9-Mediated Tissue-Specific Mutagenesis Reveals Gene Redundancy and Perdurance in .

Tissue-specific loss-of-function (LOF) analysis is essential for characterizing gene function. Here, we present a simple, yet highly efficient, clustered regularly interspaced short palindromic repeats (CRISPR)-mediated tissue-restricted mutagenesis (CRISPR-TRiM) method for ablating gene function in This binary system consists of a tissue-specific Cas9 and a ubiquitously expressed multi-guide RNA (gRNA) transgene. We describe convenient toolkits for making enhancer-driven Cas9 lines and multi-gRNAs that are optimized for mutagenizing somatic cells.

Phosphatidylserine Externalization Results from and Causes Neurite Degeneration in Drosophila.

Phagocytic clearance of degenerating dendrites or axons is critical for maintaining tissue homeostasis and preventing neuroinflammation. Externalized phosphatidylserine (PS) has been postulated to be an "eat-me" signal allowing recognition of degenerating neurites by phagocytes. Here we show that in Drosophila, PS is dynamically exposed on degenerating dendrites during developmental pruning and after physical injury, but PS exposure is suppressed when dendrite degeneration is genetically blocked.

Dendritic space-filling requires a neuronal type-specific extracellular permissive signal in .

Neurons sometimes completely fill available space in their receptive fields with evenly spaced dendrites to uniformly sample sensory or synaptic information. The mechanisms that enable neurons to sense and innervate all space in their target tissues are poorly understood. Using somatosensory neurons as a model, we show that heparan sulfate proteoglycans (HSPGs) Dally and Syndecan on the surface of epidermal cells act as local permissive signals for the dendritic growth and maintenance of space-filling nociceptive C4da neurons, allowing them to innervate the entire skin.

HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways.

Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons.

The transcriptional repressor Sum1p counteracts Sir2p in regulation of the actin cytoskeleton, mitochondrial quality control and replicative lifespan in .

Increasing the stability or dynamics of the actin cytoskeleton can extend lifespan in and . Actin cables of budding yeast, bundles of actin filaments that mediate cargo transport, affect lifespan control through effects on mitochondrial quality control. Sir2p, the founding member of the Sirtuin family of lifespan regulators, also affects actin cable dynamics, assembly, and function in mitochondrial quality control.

Fast quantitative real-time PCR-based screening for common chromosomal aneuploidies in mouse embryonic stem cells.

Chromosomal integrity has been known for many years to affect the ability of mouse embryonic stem cells (mESCs) to contribute to the germline of chimeric mice. Abnormal chromosomes are generally detected by standard cytogenetic karyotyping. However, this method is expensive, time consuming, and often omitted prior to blastocyst injection, consequently reducing the frequency of mESC-derived offspring.

β2 adrenergic receptor fluorescent protein fusions traffic to the plasma membrane and retain functionality.

Green fluorescent protein (GFP) has proven useful for the study of protein interactions and dynamics for the last twenty years. A variety of new fluorescent proteins have been developed that expand the use of available excitation spectra. We have undertaken an analysis of seven of the most useful fluorescent proteins (XFPs), Cerulean (and mCerulean3), Teal, GFP, Venus, mCherry and TagRFP657, as fusions to the archetypal G-protein coupled receptor, the β2 adrenergic receptor (β2AR).