Central nervous system (CNS) myelination by oligodendrocytes (OLs) is a highly orchestrated process involving well-defined steps from specification of neural stem cells into proliferative OL ...precursors followed by terminal differentiation and subsequent maturation of these precursors into myelinating OLs. These specification and differentiation processes are mediated by profound global changes in gene expression, which are in turn subject to control by both extracellular signals and regulatory networks intrinsic to the OL lineage. Recently, basic transcriptional mechanisms that control OL differentiation and myelination have begun to be elucidated at the molecular level and on a genome scale. The interplay between transcription factors activated by differentiation-promoting signals and master regulators likely exerts a crucial role in controlling stage-specific progression of the OL lineage. In this review, we describe the current state of knowledge regarding the transcription factors and the epigenetic programs including histone methylation, acetylation, chromatin remodeling, micro-RNAs, and noncoding RNAs that regulate development of OLs and myelination.
Volatile organic compound (VOC) species from vehicle exhausts and gas evaporation were investigated by chassis dynamometer and on-road measurements of nine gasoline vehicles, seven diesel vehicles, ...five motorcycles, and four gas evaporation samples. The secondary organic aerosol (SOA) mass yields of gasoline, diesel, motorcycle exhausts, and gas evaporation were estimated based on the mixing ratio of measured C2-C12 VOC species and inferred carbon number distributions. High aromatic contents were measured in gasoline exhausts and contributed comparatively more SOA yield. A vehicular emission inventory was compiled based on a local survey of on-road traffic in Shanghai and real-world measurements of vehicle emission factors from previous studies in the cities of China. The inventory-based vehicular organic aerosol (OA) productions to total CO emissions were compared with the observed OA to CO concentrations ( Delta OA / Delta CO) in the urban atmosphere. The results indicate that vehicles dominate the primary organic aerosol (POA) emissions and OA production, which contributed about 40 and 60 % of OA mass in the urban atmosphere of Shanghai. Diesel vehicles, which accounted for less than 20 % of vehicle kilometers of travel (VKT), contribute more than 90 % of vehicular POA emissions and 80-90 % of OA mass derived by vehicles in urban Shanghai. Gasoline exhaust could be an important source of SOA formation. Tightening the limit of aromatic content in gasoline fuel will be helpful to reduce its SOA contribution. Intermediate-volatile organic compounds (IVOCs) in vehicle exhausts greatly contribute to SOA formation in the urban atmosphere of China. However, more experiments need to be conducted to determine the contributions of IVOCs to OA pollution in China.
Maintaining fast charging capability at low temperatures represents a significant challenge for supercapacitors. The performance of conventional porous carbon electrodes often deteriorates quickly ...with the decrease of temperature due to sluggish ion and charge transport. Here we fabricate a 3D-printed multiscale porous carbon aerogel (3D-MCA) via a unique combination of chemical methods and the direct ink writing technique. 3D-MCA has an open porous structure with a large surface area of ∼1750 m2 g–1. At −70 °C, the symmetric device achieves outstanding capacitance of 148.6 F g–1 at 5 mV s–1. Significantly, it retains a capacitance of 71.4 F g–1 at a high scan rate of 200 mV s–1, which is 6.5 times higher than the non-3D printed MCA. These values rank among the best results reported for low temperature supercapacitors. These impressive results highlight the essential role of open porous structures for preserving capacitive performance at ultralow temperatures.
Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The ...basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/β-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and β-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair.
► Zinc finger homeobox transcription factor Sip1/Zfhx1b is required for CNS myelination ► Sip1 promotes CNS myelination by modulating BMP-Smad signaling activity ► Identification of a new oligodendrocyte-enriched gene Smad7 as a key Sip1 target ► Smad7 is both sufficient and critical for oligodendrocyte differentiation
Weng et al. find the transcription factor Sip1 governs myelination by modulating Smad signaling and reveal a key Sip1-induced target, Smad7, which promotes oligodendrocyte differentiation by blocking BMP and β-catenin negative regulatory pathways.
Myelination facilitates rapid axonal conduction, enabling efficient communication across different parts of the nervous system. Here we examined mechanisms controlling myelination after injury and ...during axon regeneration in the central nervous system (CNS). Previously, we discovered multiple molecular pathways and strategies that could promote robust axon regrowth after optic nerve injury. However, regenerated axons remain unmyelinated, and the underlying mechanisms are elusive. In this study, we found that, in injured optic nerves, oligodendrocyte precursor cells (OPCs) undergo transient proliferation but fail to differentiate into mature myelination-competent oligodendrocytes, reminiscent of what is observed in human progressive multiple sclerosis. Mechanistically, we showed that OPC-intrinsic GPR17 signaling and sustained activation of microglia inhibit different stages of OPC differentiation. Importantly, co-manipulation of GPR17 and microglia led to extensive myelination of regenerated axons. The regulatory mechanisms of stage-dependent OPC differentiation uncovered here suggest a translatable strategy for efficient de novo myelination after CNS injury.
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•Proliferated OPCs exhibit differentiation blockade in injured optic nerves•GPR17 inhibition promotes OPC differentiation•Chronically activated microglia prevent oligodendrocyte maturation•Co-manipulation of GPR17 and microglia promotes robust myelination
While investigating why regenerated axons fail to be myelinated in injured optic nerves, Wang et al. find that injury-induced GPR17 expression in OPCs and chronically activated microglia suppress different steps of OPC differentiation. Co-manipulation of intrinsic (GPR17) and extrinsic (microglia) factors promotes extensive myelination of regenerated axons in an inflammatory environment.
Topical application of pathogen-specific double-stranded RNA (dsRNA) for virus resistance in plants represents an attractive alternative to transgenic RNA interference (RNAi). However, the ...instability of naked dsRNA sprayed on plants has been a major challenge towards its practical application. We demonstrate that dsRNA can be loaded on designer, non-toxic, degradable, layered double hydroxide (LDH) clay nanosheets. Once loaded on LDH, the dsRNA does not wash off, shows sustained release and can be detected on sprayed leaves even 30 days after application. We provide evidence for the degradation of LDH, dsRNA uptake in plant cells and silencing of homologous RNA on topical application. Significantly, a single spray of dsRNA loaded on LDH (BioClay) afforded virus protection for at least 20 days when challenged on sprayed and newly emerged unsprayed leaves. This innovation translates nanotechnology developed for delivery of RNAi for human therapeutics to use in crop protection as an environmentally sustainable and easy to adopt topical spray.
Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is ...recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.
There is a strong desire to design and synthesize catalysts that assemble at the oil–water interface to improve the efficiency of biphasic reactions. Anisotropic dumbbell‐shaped bi‐component ...mesoporous carbon–organosilica Janus particles with asymmetric wettability are synthesized through a one‐step compartmentalized growth of a mesoporous organosilica sphere attached to a mesoporous resorcinol–formaldehyde (RF) sphere. A library was prepared of tunable Janus particles possessing diverse hollow structures with various functionalities. As a proof of concept, the Janus particle‐derived catalyst can assemble at the oil–water interface to stabilize Pickering emulsions. Owing to the increased reaction interface area, the Janus catalyst exhibits a more than three‐fold increase in catalytic efficiency compared to the Pt loaded carbon sphere catalyst in aqueous hydrogenation reactions.
Anisotropic dumbbell‐shaped bi‐component mesoporous carbon–organosilica Janus particles with asymmetric wettability were synthesized through a one‐step compartmentalized growth of a mesoporous organosilica sphere attached to a mesoporous resorcinol–formaldehyde sphere. This catalyst assembles at the oil–water interface to stabilize Pickering emulsions, resulting in catalysis efficiency enhancement in aqueous hydrogenation reactions.
Abstract
Ten-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and ...remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of
Tet1
results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking
Tet1
in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and 5-hydroxymethylcytosine (5hmC) profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport.
Tet1
-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene,
Itpr2
, impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice.
Long noncoding RNAs (lncRNAs) are emerging as important regulators of cellular functions, but their roles in oligodendrocyte myelination remain undefined. Through de novo transcriptome ...reconstruction, we establish dynamic expression profiles of lncRNAs at different stages of oligodendrocyte development and uncover a cohort of stage-specific oligodendrocyte-restricted lncRNAs, including a conserved chromatin-associated lncOL1. Co-expression network analyses further define the association of distinct oligodendrocyte-expressing lncRNA clusters with protein-coding genes and predict lncRNA functions in oligodendrocyte myelination. Overexpression of lncOL1 promotes precocious oligodendrocyte differentiation in the developing brain, whereas genetic inactivation of lncOL1 causes defects in CNS myelination and remyelination following injury. Functional analyses illustrate that lncOL1 interacts with Suz12, a component of polycomb repressive complex 2, to promote oligodendrocyte maturation, in part, through Suz12-mediated repression of a differentiation inhibitory network that maintains the precursor state. Together, our findings reveal a key lncRNA epigenetic circuitry through interaction with chromatin-modifying complexes in control of CNS myelination and myelin repair.
•Transcriptome reconstruction reveals a dynamic network of lncRNAs in oligodendrocytes•Identification of oligodendrocyte-enriched lncOLs critical for OPC differentiation•Oligodendrocyte-restricted lncOL1 regulates timely CNS myelination and remyelination•lncOL1 interacts with Suz12-PRC2 complex to orchestrate OPC differentiation program
He et al. describe an integrated transcriptional map of lncRNA networks at multiple stages during oligodendrocyte lineage progression and reveal a key lncRNA epigenetic circuitry through interaction with chromatin-modifying complexes in control of CNS myelination and myelin repair.
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