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1.
Nat Commun ; 11(1): 2023, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332726

RESUMO

The Seebeck effect converts thermal gradients into electricity. As an approach to power technologies in the current Internet-of-Things era, on-chip energy harvesting is highly attractive, and to be effective, demands thin film materials with large Seebeck coefficients. In spintronics, the antiferromagnetic metal IrMn has been used as the pinning layer in magnetic tunnel junctions that form building blocks for magnetic random access memories and magnetic sensors. Spin pumping experiments revealed that IrMn Néel temperature is thickness-dependent and approaches room temperature when the layer is thin. Here, we report that the Seebeck coefficient is maximum at the Néel temperature of IrMn of 0.6 to 4.0 nm in thickness in IrMn-based half magnetic tunnel junctions. We obtain a record Seebeck coefficient 390 (±10) µV K-1 at room temperature. Our results demonstrate that IrMn-based magnetic devices could harvest the heat dissipation for magnetic sensors, thus contributing to the Power-of-Things paradigm.

2.
Nano Lett ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32227904

RESUMO

Spin-orbit torque (SOT) switching of magnetization is a promising emerging technology for nonvolatile spintronic memory and logic applications. However, deterministic switching of perpendicular magnetization with SOTs requires an additional symmetry breaking, which is typically provided by an external magnetic field, making it impractical for applications. In this work, we disclose that by the insertion of a slightly asymmetric light-metal layer at the heavy metal-ferromagnet interface of SOT heterostructures, current-induced out-of-plane effective magnetic fields are introduced that enable deterministic switching without an external magnetic field. We obtain uniform perpendicular magnetic anisotropy and switching current density despite the asymmetry of the light-metal layer, and we show the scalability of our approach by studying device sizes that differ by 2 orders of magnitude. Our work provides a practical route for utilization of SOTs for magnetization switching on the wafer scale and paves the way for the practical application of SOT-based technology.

3.
Adv Mater ; : e2000513, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32176423

RESUMO

Manipulation of magnetization by electric-current-induced spin-orbit torque (SOT) is of great importance for spintronic applications because of its merits in energy-efficient and high-speed operation. An ideal material for SOT applications should possess high charge-spin conversion efficiency and high electrical conductivity. Recently, transition metal dichalcogenides (TMDs) emerge as intriguing platforms for SOT study because of their controllability in spin-orbit coupling, conductivity, and energy band topology. Although TMDs show great potentials in SOT applications, the present study is restricted to the mechanically exfoliated samples with small sizes and relatively low conductivities. Here, a manufacturable recipe is developed to fabricate large-area thin films of PtTe2 , a type-II Dirac semimetal, to study their capability of generating SOT. Large SOT efficiency together with high conductivity results in a giant spin Hall conductivity of PtTe2 thin films, which is the largest value among the presently reported TMDs. It is further demonstrated that the SOT from PtTe2 layer can switch a perpendicularly magnetized CoTb layer efficiently. This work paves the way for employing PtTe2 -like TMDs for wafer-scale spintronic device applications.

4.
J Proteome Res ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32202800

RESUMO

Coronary artery disease remains a leading cause of death in industrialized nations, and early detection of disease is a critical intervention target to effectively treat patients and manage risk. Proteomic analysis of mixed tissue homogenates may obscure subtle protein changes that occur uniquely in underlying tissue subtypes. The unsupervised 'convex analysis of mixtures' (CAM) tool has previously been shown to effectively segregate cellular subtypes from mixed expression data. In this study, we hypothesized that CAM would identify proteomic information specifically informative to early atherosclerosis lesion involvement that could lead to potential markers of early disease detection. We quantified the proteome of 99 paired abdominal aorta (AA) and left anterior descending coronary artery (LAD) specimens (N = 198 specimens total) acquired during autopsy of young adults free of diagnosed cardiac disease. The CAM tool was then used to segregate protein subsets uniquely associated with different underlying tissue types, yielding markers of normal and fibrous plaque (FP) tissues in LAD and AA (N = 62 lesions markers). CAM-derived FP marker expression was validated against pathologist estimated luminal surface involvement of FP, as well as in an orthogonal cohort of "pure" fibrous plaque, fatty streak, and normal vascular specimens. A targeted mass spectrometry (MS) assay quantified 39 of 62 CAM-FP markers in plasma from women with angiographically verified coronary artery disease (CAD, N = 46) or free from apparent CAD (control, N = 40). Elastic net variable selection with logistic regression reduced this list to 10 proteins capable of classifying CAD status in this cohort with <6% misclassification error, and a mean area under the receiver operating characteristic curve of 0.992 (confidence interval 0.968-0.998) after cross validation. The proteomics-CAM workflow identified lesion-specific molecular biomarker candidates by distilling the most representative molecules from heterogeneous tissue types.

5.
Biomed Pharmacother ; 122: 109557, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918265

RESUMO

Prostate cancer (PCa) is a destructive malignancy with a bad prognosis. LncRNA VPS9D1-AS1 has recently been delineated as an oncogene in some kinds of tumor, whereas, the function of VPS9D1-AS1 in PCa remains to be clarified. In this study, we researched its underlying role in PCa. The expression of VPS9D1-AS1 was conspicuously upregulated in PCa tissues and cells. And absence of VPS9D1-AS1 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in PCa. In addition, VPS9D1-AS1 overexpression led to opposite results. Furthermore, VPS9D1-AS1/MEF2D could sponge with miR-4739. VPS9D1-AS1/MEF2D and miR-4739 were inversely correlated in tumor cells. And the expression of miR-4739 is markedly downregulated in PCa, meanwhile, that of MEF2D exhibited the opposite tendency. However, MEF2D was positively regulated by VPS9D1-AS1. Moreover, MEF2D upregulation offset the suppressive effects of VPS9D1-AS1 deficiency on cell proliferation, migration and invasion in PCa. Additionally, ZEB1 contained the binding sites of VPS9D1-AS1 promoter, and there existed positive relation between them. Taken together, above results illustrated that ZEB1 activated-VPS9D1-AS1 promotes the tumorigenesis and progression of PCa by sponging miR-4739 to upregulate MEF2D, which offering a new useful reference for studying the development process of PCa.

6.
Bioinformatics ; 36(9): 2862-2871, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31950989

RESUMO

MOTIVATION: Liquid chromatography-mass spectrometry (LC-MS) is a standard method for proteomics and metabolomics analysis of biological samples. Unfortunately, it suffers from various changes in the retention times (RT) of the same compound in different samples, and these must be subsequently corrected (aligned) during data processing. Classic alignment methods such as in the popular XCMS package often assume a single time-warping function for each sample. Thus, the potentially varying RT drift for compounds with different masses in a sample is neglected in these methods. Moreover, the systematic change in RT drift across run order is often not considered by alignment algorithms. Therefore, these methods cannot effectively correct all misalignments. For a large-scale experiment involving many samples, the existence of misalignment becomes inevitable and concerning. RESULTS: Here, we describe an integrated reference-free profile alignment method, neighbor-wise compound-specific Graphical Time Warping (ncGTW), that can detect misaligned features and align profiles by leveraging expected RT drift structures and compound-specific warping functions. Specifically, ncGTW uses individualized warping functions for different compounds and assigns constraint edges on warping functions of neighboring samples. Validated with both realistic synthetic data and internal quality control samples, ncGTW applied to two large-scale metabolomics LC-MS datasets identifies many misaligned features and successfully realigns them. These features would otherwise be discarded or uncorrected using existing methods. The ncGTW software tool is developed currently as a plug-in to detect and realign misaligned features present in standard XCMS output. AVAILABILITY AND IMPLEMENTATION: An R package of ncGTW is freely available at Bioconductor and https://github.com/ChiungTingWu/ncGTW. A detailed user's manual and a vignette are provided within the package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

7.
Mil Med ; 185(Supplement_1): 82-87, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31498406

RESUMO

INTRODUCTION: Tissue injuries are often associated with abnormal blood flow (BF). The ability to assess BF distributions in injured tissues enables objective evaluation of interventions and holds the potential to improve the acute management of these injuries on battlefield. MATERIALS AND METHODS: We have developed a novel speckle contrast diffuse correlation tomography (scDCT) system for noncontact 3D imaging of tissue BF distributions. In scDCT, a galvo mirror was used to remotely project near-infrared point light to different source positions and an electron multiplying charge-coupled-device was used to detect boundary diffuse speckle contrasts. The normalized boundary data were then inserted into a modified Near-Infrared Fluorescence and Spectral Tomography program for 3D reconstructions of BF distributions. This article reports the first application of scDCT for noncontact 3D imaging of BF distributions in burn wounds. RESULTS: Significant lower BF values were observed in the burned areas/volumes compared to surrounding normal tissues. CONCLUSIONS: The unique noncontact 3D imaging capability makes the scDCT applicable for intraoperative assessment of burns/wounds, without risk of infection and without interfering with sterility of the surgical field. The portable scDCT device holds the potential to be used by surgeons in combat surgical hospitals to improve the acute management of battlefield burn injuries.

8.
Nat Neurosci ; 23(2): 167-171, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31873194

RESUMO

Sex is a key modifier of neurological disease outcomes. Microglia are implicated in neurological diseases and modulated by microRNAs, but it is unknown whether microglial microRNAs have sex-specific influences on disease. We show in mice that microglial microRNA expression differs in males and females and that loss of microRNAs leads to sex-specific changes in the microglial transcriptome and tau pathology. These findings suggest that microglial microRNAs influence tau pathogenesis in a sex-specific manner.


Assuntos
Encéfalo/patologia , MicroRNAs/metabolismo , Microglia/metabolismo , Caracteres Sexuais , Tauopatias/patologia , Animais , Encéfalo/metabolismo , Feminino , Masculino , Camundongos , Microglia/patologia , Tauopatias/metabolismo , Transcriptoma , Proteínas tau/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-31666792

RESUMO

Continuous and longitudinal monitoring of cerebral blood flow (CBF) in animal models provides information for studying the mechanisms and interventions of various cerebral diseases. Since anesthesia may affect brain hemodynamics, researchers have been seeking wearable devices for use in conscious animals. We present a wearable diffuse speckle contrast flowmeter (DSCF) probe for monitoring CBF variations in mice. The DSCF probe consists of a small low-power near-infrared laser diode as a point source and an ultra-small low-power CMOS camera as a 2D detector array, which can be affixed on a mouse head. The movement of red blood cells in brain cortex (i.e., CBF) produces spatial fluctuations of laser speckles, which are captured by the camera. The DSCF system was calibrated using tissue phantoms and validated in a human forearm and mouse brains for continuous monitoring of blood flow increases and decreases against the established technologies. Significant correlations were observed among these measurements (R2 ≥ 0.80, p < 10-5). This small fiberless probe has the potential to be worn by a freely moving conscious mouse. Moreover, the flexible source-detector configuration allows for varied probing depths up to ~8 mm, which is sufficient for transcranially detecting CBF in the cortices of rodents and newborn infants.

10.
Nano Lett ; 19(12): 8621-8629, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31697502

RESUMO

Magnetic tunnel junctions (MTJs) capable of electrical read and write operations have emerged as a canonical building block for nonvolatile memory and logic. However, the cause of the widespread device properties found experimentally in various MTJ stacks, including tunneling magnetoresistance (TMR), perpendicular magnetic anisotropy (PMA), and voltage-controlled magnetic anisotropy (VCMA), remains elusive. Here, using high-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy, we found that the MTJ crystallization quality, boron diffusion out of the CoFeB fixed layer, and minimal oxidation of the fixed layer correlate with the TMR. As with the CoFeB free layer, seed layer diffusion into the free layer/MgO interface is negatively correlated with the interfacial PMA, whereas the metal-oxides concentrations in the free layer correlate with the VCMA. Combined with formation enthalpy and thermal diffusion analysis that can explain the evolution of element distribution from MTJ stack designs and annealing temperatures, we further established a predictive materials design framework to guide the complex design space explorations for high-performance MTJs. On the basis of this framework, we demonstrate experimentally high PMA and VCMA values of 1.74 mJ/m2 and 115 fJ/V·m-1 with annealing stability above 400 °C.

11.
Bioinformatics ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596456

RESUMO

MOTIVATION: Synapses are essential to neural signal transmission. Therefore, quantification of synapses and related neurites from images is vital to gain insights into the underlying pathways of brain functionality and diseases. Despite the wide availability of synaptic punctum imaging data, several issues are impeding satisfactory quantification of these structures by current tools. First, the antibodies used for labeling synapses are not perfectly specific to synapses. These antibodies may exist in neurites or other cell compartments. Second, the brightness of different neurites and synaptic puncta is heterogeneous due to the variation of antibody concentration and synapse-intrinsic differences. Third, images often have low signal to noise ratio due to constraints of experiment facilities and availability of sensitive antibodies. These issues make the detection of synapses challenging and necessitates developing a new tool to easily and accurately quantify synapses. RESULTS: We present an automatic probability-principled synapse detection algorithm and integrate it into our synapse quantification tool SynQuant. Derived from the theory of order statistics, our method controls the false discovery rate and improves the power of detecting synapses. SynQuant is unsupervised, works for both 2D and 3D data, and can handle multiple staining channels. Through extensive experiments on one synthetic and three real data sets with ground truth annotation or manually labeling, SynQuant was demonstrated to outperform peer specialized unsupervised synapse detection tools as well as generic spot detection methods. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Java source code, Fiji plug-in, and test data are available at https://github.com/yu-lab-vt/SynQuant.

12.
Nat Neurosci ; 22(11): 1936-1944, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31570865

RESUMO

Recent work examining astrocytic physiology centers on fluorescence imaging, due to development of sensitive fluorescent indicators and observation of spatiotemporally complex calcium activity. However, the field remains hindered in characterizing these dynamics, both within single cells and at the population level, because of the insufficiency of current region-of-interest-based approaches to describe activity that is often spatially unfixed, size-varying and propagative. Here we present an analytical framework that releases astrocyte biologists from region-of-interest-based tools. The Astrocyte Quantitative Analysis (AQuA) software takes an event-based perspective to model and accurately quantify complex calcium and neurotransmitter activity in fluorescence imaging datasets. We apply AQuA to a range of ex vivo and in vivo imaging data and use physiologically relevant parameters to comprehensively describe the data. Since AQuA is data-driven and based on machine learning principles, it can be applied across model organisms, fluorescent indicators, experimental modes, and imaging resolutions and speeds, enabling researchers to elucidate fundamental neural physiology.


Assuntos
Astrócitos/metabolismo , Cálcio/metabolismo , Processamento de Imagem Assistida por Computador/métodos , Neurotransmissores/metabolismo , Imagem Óptica/métodos , Adenoviridae , Algoritmos , Animais , Animais Recém-Nascidos , Vetores Genéticos , Camundongos , Software , Transfecção , Córtex Visual/metabolismo
14.
PLoS Biol ; 17(8): e3000086, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31433818

RESUMO

Lengthy use of general anesthetics (GAs) causes neurobehavioral deficits in the developing brain, which has raised significant clinical concerns such that the United States Food and Drug Administration (FDA) is warning on the use of GAs in children younger than 3 years. However, the molecular and cellular mechanisms for GAs-induced neurotoxicity remain largely unknown. Here, we report that sevoflurane (Sevo), a commonly used GA in pediatrics, caused compromised astrocyte morphogenesis spatiotemporally correlated to synaptic overgrowth, with reduced synaptic function in developing cortex in a regional-, exposure-length-, and age-specific manner. Sevo disrupted astrocyte Ca2+ homeostasis both acutely and chronically, which led to the down-regulation of Ezrin, an actin-binding membrane-bound protein, which we found was critically involved in astrocyte morphogenesis in vivo. Importantly, overexpression of astrocyte Ezrin rescued astrocytic and neuronal dysfunctions and fully corrected deficits in social behaviors in developing mice with lengthy Sevo exposure. Our data uncover that, in addition to neurons, astrocytes may represent important targets for GAs to exert toxic effects and that astrocyte morphological integrity is crucial for synaptogenesis and neurological behaviors.


Assuntos
Astrócitos/efeitos dos fármacos , Sevoflurano/efeitos adversos , Sinapses/efeitos dos fármacos , Anestesia Geral/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Animais , Animais Recém-Nascidos , Comportamento Animal , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Proteínas do Citoesqueleto/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Comportamento Social
15.
Sci Adv ; 5(8): eaaw8904, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31467976

RESUMO

The recent discovery of ferromagnetism in two-dimensional (2D) van der Waals (vdW) materials holds promises for spintronic devices with exceptional properties. However, to use 2D vdW magnets for building spintronic nanodevices such as magnetic memories, key challenges remain in terms of effectively switching the magnetization from one state to the other electrically. Here, we devise a bilayer structure of Fe3GeTe2/Pt, in which the magnetization of few-layered Fe3GeTe2 can be effectively switched by the spin-orbit torques (SOTs) originated from the current flowing in the Pt layer. The effective magnetic fields corresponding to the SOTs are further quantitatively characterized using harmonic measurements. Our demonstration of the SOT-driven magnetization switching in a 2D vdW magnet could pave the way for implementing low-dimensional materials in the next-generation spintronic applications.

16.
Adv Mater ; 31(35): e1901681, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282067

RESUMO

Utilizing spin-orbit torque (SOT) to switch a magnetic moment provides a promising route for low-power-dissipation spintronic devices. Here, the SOT switching of a nearly compensated ferrimagnet Gdx (FeCo)1- x by the topological insulator [Bi2 Se3 and (BiSb)2 Te3 ] is investigated at room temperature. The switching current density of (BiSb)2 Te3 (1.20 × 105 A cm-2 ) is more than one order of magnitude smaller than that in conventional heavy-metal-based structures, which indicates the ultrahigh efficiency of charge-spin conversion (>1) in topological surface states. By tuning the net magnetic moment of Gdx (FeCo)1- x via changing the composition, the SOT efficiency has a significant enhancement (6.5 times) near the magnetic compensation point, and at the same time the switching speed can be as fast as several picoseconds. Combining the topological surface states and the nearly compensated ferrimagnets provides a promising route for practical energy-efficient and high-speed spintronic devices.

17.
R Soc Open Sci ; 6(5): 181686, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31218024

RESUMO

In order to enhance the ignition ability and reliability of traditional electronic initiators, a novel electronic initiator has been designed to integrate with a nanothermite multilayer film and an electrode plug. The Al/CuOx nanothermite multilayer film with different thickness is deposited on the surface of the electrode plug by magnetron sputtering which uses Pt-W wire as electronic resistance. The exothermicity of Al/CuOx nanothermite multilayer film is so favourable that the ignition ability of electronic initiator is significantly improved. The full firing-voltage sensitivity of the electronic initiator is 10.8 V. The thickness of Al/CuOx multilayer film has negligible effects on the ignition time and ignition energy, but leads to great impacts on the function time, the maximum length of combustion flame and ignition ability. The electrical ignition experiments have exhibited outstanding ignition ability, since the electronic initiator can easily fire the insensitive ignition composition of boron-potassium nitrate (B-KNO3) tablet in a gap of 20.35 mm. It proves that this novel proposal of remoulding the traditional electronic ignition devices will distinctly improve the ignition ability and reliability of electronic initiator.

18.
Biomed Pharmacother ; 117: 109109, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31229922

RESUMO

Prostate carcinoma may develop into metastatic castration-resistant prostate carcinoma (mCRPC) after endocrine therapy. Exosomal microRNAs play an important role in the regulation of tumor microenvironment. Our study aimed to investigate the effect of exosomal miR-26a on tumor phenotype of prostate carcinoma. Low-grade prostate carcinoma cell line (LNCAP) and mCRPC cell line (PC-3) were treated as experimental subjects according to their miR-26a expressions. Wound healing, transwell and colony-forming unit assays were performed after miR-26a mimic/inhibitor transfection. Then, exosomes were isolated from LNCAP and PC-3 cells, and the levels of exosomal miR-26a were determined. After co-culture of LNCAP (PC-3) cells with PC-3 (LNCAP) exosomes, changes in malignant behaviors were measured. Moreover, LNCAP/PC-3 exosomes were injected into xenograft tumor mice to determine effects of the exosomes on tumorigenicity of LNCAP and PC-3 cells. MiR-26a showed a potently inhibitory effect on cell proliferation, migration and invasion of LNCAP and PC-3 cells. LNCAP exosomes had a higher miR-26a level, compared with PC-3 exosomes. Overexpression of miR-26a attenuated the enhanced malignant behavior of LNCAP cells induced by PC-3 exosomes, and miR-26a inhibition could reverse the inhibitory effects of LNCAP exosomes on PC-3 cells. Exosomal miR-26a could significantly alter the expressions of epithelial-mesenchymal transition (EMT)-related factors. Moreover, LNCAP exosomes suppressed the tumorigenicity of PC-3 cells, while PC-3 exosomes could promote the tumorigenicity of LNCAP cells. Our data suggest that exosomal miR-26a derived from prostate carcinoma cells had a suppressive effect on the metastasis and tumor growth of prostate carcinoma.


Assuntos
Exossomos/metabolismo , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Exossomos/ultraestrutura , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Metástase Neoplásica
19.
Neuroimage ; 198: 160-169, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31112789

RESUMO

Continuous and longitudinal imaging of cerebral blood flow (CBF) variations provide vital information to investigate pathophysiology and interventions for a variety of neurological and cerebral diseases. An innovative noncontact speckle contrast diffuse correlation tomography (scDCT) system was downscaled and adapted for noninvasive imaging of CBF distributions in rat brain through intact scalp and skull. Algorithms for 2D mapping and 3D image reconstruction of CBF distributions were developed and optimized. The continuous imaging capability of the system was shown by imaging global CBF increases during CO2 inhalations and regional CBF decreases across two hemispheres during sequential unilateral and bilateral common carotid artery ligations. The longitudinal imaging capability was demonstrated by imaging CBF variations over a long recovery period of 14 days after an acute stroke. Compared to the 2D mapping method, the 3D imaging method reduces partial volume effects, but needs more computation time for image reconstruction. Results from this study generally agree with those reported in the literature using similar protocols to induce CBF changes in rats. The scDCT enables a relatively large penetration depth (up to ∼10 mm), which is sufficient for transcranial brain measurements in small animals and human neonates. Ultimately, we expect to provide a noninvasive noncontact cerebral imager for basic neuroscience research in small animal models and clinical applications in human neonates.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Imagem Óptica/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia/métodos , Animais , Encéfalo/fisiopatologia , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Imageamento Tridimensional/métodos , Masculino , Imagem Óptica/instrumentação , Ratos Sprague-Dawley , Acidente Vascular Cerebral/fisiopatologia , Tomografia/instrumentação
20.
Cell Stem Cell ; 24(5): 707-723.e8, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30982771

RESUMO

The identity and degree of heterogeneity of glial progenitors and their contributions to brain tumor malignancy remain elusive. By applying lineage-targeted single-cell transcriptomics, we uncover an unanticipated diversity of glial progenitor pools with unique molecular identities in developing brain. Our analysis identifies distinct transitional intermediate states and their divergent developmental trajectories in astroglial and oligodendroglial lineages. Moreover, intersectional analysis uncovers analogous intermediate progenitors during brain tumorigenesis, wherein oligodendrocyte-progenitor intermediates are abundant, hyper-proliferative, and progressively reprogrammed toward a stem-like state susceptible to further malignant transformation. Similar actively cycling intermediate progenitors are prominent components in human gliomas with distinct driver mutations. We further unveil lineage-driving networks underlying glial fate specification and identify Zfp36l1 as necessary for oligodendrocyte-astrocyte lineage transition and glioma growth. Together, our results resolve the dynamic repertoire of common and divergent glial progenitors during development and tumorigenesis and highlight Zfp36l1 as a molecular nexus for balancing glial cell-fate decision and controlling gliomagenesis.

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