scholarly journals A role for the P2Y1 receptor in nonsynaptic cross-depolarization in the rat dorsal root ganglia

2019 ◽  
Author(s):  
Gil B. Carvalho ◽  
Yatendra Mulpuri ◽  
Antonio Damasio ◽  
Igor Spigelman
Keyword(s):  
Glial Cells ◽  
Dorsal Root ◽  
Purinergic Receptor ◽  
Extracellular Calcium ◽  
Nodose Ganglion ◽  
Chemical Agent ◽  
List Type ◽  
C Cells ◽  
Cell Type ◽  
Cell Type Specific

AbstractNon-synaptic transmission is pervasive throughout the nervous system. It appears especially prevalent in peripheral ganglia, where non-synaptic interactions between neighboring cell bodies have been described in both physiological and pathological conditions, a phenomenon referred to as cross-depolarization (CD) and thought to play a role in sensory processing and chronic pain. CD has been proposed to be mediated by a chemical agent, but its identity has remained elusive. Here, we report that in the rat dorsal root ganglion (DRG), the P2Y1 purinergic receptor (P2RY1) plays an important role in regulating CD. The effect of P2RY1 is cell-type specific: pharmacological blockade of P2RY1 inhibited CD in A-type neurons while enhancing it in unmyelinated C-type cells. In the nodose ganglion of the vagus, CD requires extracellular calcium in a large percentage of cells. In contrast, we show that in the DRG extracellular calcium appears to play no major role, pointing to a mechanistic difference between the two peripheral ganglia. Furthermore, we show that DRG glial cells also play a cell-type specific role in CD regulation. Fluorocitrate-induced glial inactivation had no effect on A-cells but enhanced CD in C-cells. These findings shed light on the mechanism of CD in the DRG and pave the way for further analysis of non-synaptic neuronal communication in sensory ganglia.HighlightsThe purinergic receptor P2RY1 plays a regulatory role in non-synaptic crossdepolarization (CD) in the mammalian DRGThe effect of P2RY1 is cell type-specific: it enhances CD in myelinated A-type neurons, but inhibits it in unmyelinated C-cellsCD in the DRG does not require extracellular calcium. This is in contrast with the nodose ganglion, where extracellular calcium plays an important role in nonsynaptic interactionsCD is also modulated by DRG glial cells. Glia selectively inhibit CD in C-type neurons

scholarly journals FIREcaller: Detecting Frequently Interacting Regions from Hi-C Data

2019 ◽  
Author(s):  
Cheynna Crowley ◽  
Yuchen Yang ◽  
Yunjiang Qiu ◽  
Benxia Hu ◽  
Armen Abnousi ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Spatial Organization ◽  
R Package ◽  
Specific Gene ◽  
List Type ◽  
Cell Type ◽  
R Software ◽  
Computational Tools ◽  
Cell Type Specific ◽  
User Friendly

AbstractHi-C experiments have been widely adopted to study chromatin spatial organization, which plays an essential role in genome function. We have recently identified frequently interacting regions (FIREs) and found that they are closely associated with cell-type-specific gene regulation. However, computational tools for detecting FIREs from Hi-C data are still lacking. In this work, we present FIREcaller, a stand-alone, user-friendly R package for detecting FIREs from Hi-C data. FIREcaller takes raw Hi-C contact matrices as input, performs within-sample and cross-sample normalization, and outputs continuous FIRE scores, dichotomous FIREs, and super-FIREs. Applying FIREcaller to Hi-C data from various human tissues, we demonstrate that FIREs and super-FIREs identified, in a tissue-specific manner, are closely related to gene regulation, are enriched for enhancer-promoter (E-P) interactions, tend to overlap with regions exhibiting epigenomic signatures of cis-regulatory roles, and aid the interpretation or GWAS variants. The FIREcaller package is implemented in R and freely available at https://yunliweb.its.unc.edu/FIREcaller.Highlights– Frequently Interacting Regions (FIREs) can be used to identify tissue and cell-type-specific cis-regulatory regions.– An R software, FIREcaller, has been developed to identify FIREs and clustered FIREs into super-FIREs.

scholarly journals Oligodendrocytes and Microglia Are Selectively Vulnerable to Combined Hypoxia and Hypoglycemia Injury in Vitro

1998 ◽  
Vol 18 (5) ◽  
pp. 521-530 ◽  
Author(s):  
Susan A. Lyons ◽  
Helmut Kettenmann
Keyword(s):  
Lactate Dehydrogenase ◽  
Glial Cell ◽  
Glial Cells ◽  
Cell Types ◽  
Neonatal Rat ◽  
Radical Scavenger ◽  
Cell Type ◽  
Hypoxic Conditions ◽  
Cell Type Specific

The major classes of glial cells, namely astrocytes, oligodendrocytes, and microglial cells were compared in parallel for their susceptibility to damage after combined hypoxia and hypoglycemia or hypoxia alone. The three glial cell types were isolated from neonatal rat brains, separated, and incubated in N2/CO2-gassed buffer-containing glucose or glucose substitutes, 2-deoxyglucose or mannitol (both nonmetabolizable sugars). The damage to the cells after 6 hours' exposure was determined at 0, 1, 3, 7 days based on release of lactate dehydrogenase and counting of ethidium bromide–stained dead cells, double-stained with cell-type specific markers. When 2-deoxyglucose replaced glucose during 6 hours of hypoxia, both oligodendrocytes and microglia rarely survived (18% and 12%, respectively). Astroglia initially increased the release of lactate dehydrogenase but maintained 98% to 99% viability. When mannitol, a radical scavenger and osmolarity stabilizer, replaced glucose during 6 hours of hypoxia, oligodendrocytes rarely survived (10%), astroglia survival remained at 99%, but microglia survival increased to 50%. After exposure to 6 and 42 hours, respectively, of hypoxic conditions alone, oligodendrocytes exhibited 10% survival whereas microglia and astroglia were only temporarily stressed and subsequently survived. In conclusion, oligodendrocytes, then microglia, are the most vulnerable glial cell types in response to hypoxia or hypoglycemia conditions, whereas astrocytes from the same preparations recover.

scholarly journals Myeloid lncRNA LOUP Mediates Opposing Regulatory Effects of RUNX1 and RUNX1-ETO in t(8;21) AML

2020 ◽  
Author(s):  
Bon Q. Trinh ◽  
Simone Ummarino ◽  
Alexander K. Ebralidze ◽  
Emiel van der Kouwe ◽  
Mahmoud A. Bassal ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Growth ◽  
Noncoding Rna ◽  
Gene Activation ◽  
Chromatin Accessibility ◽  
Myeloid Differentiation ◽  
Specific Gene ◽  
List Type ◽  
Cell Type ◽  
Cell Type Specific

ABSTRACTThe mechanism underlying cell type-specific gene induction conferred by ubiquitous transcription factors as well as disruptions caused by their chimeric derivatives in leukemia is not well understood. Here we investigate whether RNAs coordinate with transcription factors to drive myeloid gene transcription. In an integrated genome-wide approach surveying for gene loci exhibiting concurrent RNA- and DNA-interactions with the broadly expressed transcription factor RUNX1, we identified the long noncoding RNA LOUP. This myeloid-specific and polyadenylated lncRNA induces myeloid differentiation and inhibits cell growth, acting as a transcriptional inducer of the myeloid master regulator PU.1. Mechanistically, LOUP recruits RUNX1 to both the PU.1 enhancer and the promoter, leading to the formation of an active chromatin loop. In t(8;21) acute myeloid leukemia, wherein RUNX1 is fused to ETO, the resulting oncogenic fusion protein RUNX1-ETO limits chromatin accessibility at the LOUP locus, causing inhibition of LOUP and PU.1 expression. These findings highlight the important role of the interplay between cell type-specific RNAs and transcription factors as well as their oncogenic derivatives in modulating lineage-gene activation and raise the possibility that RNA regulators of transcription factors represent alternative targets for therapeutic development.KEY POINTSlncRNA LOUP coordinates with RUNX1 to induces PU.1 long-range transcription, conferring myeloid differentiation and inhibiting cell growth.RUNX1-ETO limits chromatin accessibility at the LOUP locus, causing inhibition of LOUP and PU.1 expression in t(8;21) AML.

The appearance of neural and glial cell markers during early development of the nervous system in the amphibian embryo

Development ◽  
1989 ◽  
Vol 107 (1) ◽  
pp. 43-54 ◽  
Author(s):  
N.J. Messenger ◽  
A.E. Warner
Keyword(s):  
Nervous System ◽  
Glial Cell ◽  
Glial Cells ◽  
Cell Type ◽  
Neurofilament Protein ◽  
Amphibian Embryo ◽  
Specific Antibodies ◽  
Cell Type Specific ◽  
Radial Glial ◽  
The Brain

Cell-type-specific antibodies have been used to follow the appearance of neurones and glia in the developing nervous system of the amphibian embryo. Differentiated neurones were recognized with antibodies against neurofilament protein while glial cells were identified with antibodies against glial fibrillary acidic protein (GFAP). The appearance of neurones containing the neurotransmitters 5-hydroxytryptamine and dopamine has been charted also. In Xenopus, neurofilament protein in developing neurones was observed occasionally at NF stage 21 and was present reliably in the neural tube and in caudal regions of the brain at stage 23. Antibodies to the low molecular weight fragment of the neurofilament triplet recognized early neurones most reliably. Radial glial cells, identified with GFAP antibody, were identified from stage 23 onwards in the neural tube and caudal regions of the brain. In the developing spinal cord, GFAP staining was apparent throughout the cytoplasm of each radial glial cell. In the brain, the peripheral region only of each glial cell contained GFAP. By stage 36, immunohistochemically recognizable neurones and glia were present throughout the nervous system. In the axolotl, by stage 36 the pattern of neural and glial staining was identical to that observed in Xenopus. GFAP staining of glial cells was obvious at stage 23, although neuronal staining was clearly absent. This implies that glial cells differentiate before neurones. 5-HT-containing cell bodies were first observed in caudal regions of the developing brain on either side of the midline at stage 26. An extensive network of 5-HT neurones appeared gradually, with a substantial subset crossing to the opposite side of the brain through the developing optic chiasma. 5,7-dihydroxytryptamine prevented the appearance of 5-HT. Depletion of 5-HT had little effect on development or swimming behaviour. Dopamine-containing neurones in the brain first differentiated at stage 35–36 and gradually increased in number up to stage 45–47, the latest stage examined. The functional role of 5-HT- or dopamine-containing neurones remains to be elucidated. We conclude that cell-type-specific antibodies can be used to identify neurones and glial cells at early times during neural development and may be useful tools in circumstances where functional identification is difficult.

Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture

1979 ◽  
Vol 174 (2) ◽  
pp. 283-308 ◽  
Author(s):  
Martin C. Raff ◽  
Kay L. Fields ◽  
Sen-Itiroh Hakomori ◽  
Rhona Mirsky ◽  
Rebecca M. Pruss ◽  
...  
Keyword(s):  
Glial Cells ◽  
Cell Type ◽  
Cells In Culture ◽  
Cell Type Specific

scholarly journals Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons

1999 ◽  
Vol 126 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Shinya Ueno ◽  
Makoto Tsuda ◽  
Toshihiko Iwanaga ◽  
Kazuhide Inoue
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Cell Type ◽  
Cell Type Specific ◽  
Ganglion Neurons

Cell type-specific circular RNA expression in human glial cells

Genomics ◽  
2020 ◽  
Vol 112 (6) ◽  
pp. 5265-5274
Author(s):  
Ashton Curry-Hyde ◽  
Lachlan G. Gray ◽  
Bei Jun Chen ◽  
Uwe Ueberham ◽  
Thomas Arendt ◽  
...  
Keyword(s):  
Glial Cells ◽  
Circular Rna ◽  
Rna Expression ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals Single-cell transcriptomics characterizes cell types in the subventricular zone and uncovers molecular defects underlying impaired adult neurogenesis

2018 ◽  
Author(s):  
Vera Zywitza ◽  
Aristotelis Misios ◽  
Lena Bunatyan ◽  
Thomas E. Willnow ◽  
Nikolaus Rajewsky
Keyword(s):  
Single Cell ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Single Cells ◽  
Cell Types ◽  
Neural Cell ◽  
Adult Brain ◽  
List Type ◽  
Cell Type ◽  
Cell Type Specific

SUMMARYNeural stem cells (NSCs) contribute to plasticity and repair of the adult brain. Niches harboring NSCs are crucial for regulating stem cell self-renewal and differentiation. We used single-cell RNA profiling to generate an unbiased molecular atlas of all cell types in the largest neurogenic niche of the adult mouse brain, the subventricular zone (SVZ). We characterized > 20 neural and non-neural cell types and gained insights into the dynamics of neurogenesis by predicting future cell states based on computational analysis of RNA kinetics. Furthermore, we apply our single-cell approach to mice lacking LRP2, an endocytic receptor required for SVZ maintenance. The number of NSCs and proliferating progenitors was significantly reduced. Moreover, Wnt and BMP4 signaling was perturbed. We provide a valuable resource for adult neurogenesis, insights into SVZ neurogenesis regulation by LRP2, and a proof-of-principle demonstrating the power of single-cell RNA-seq in pinpointing neural cell type-specific functions in loss-of-function models.HIGHLIGHTSunbiased single-cell transcriptomics characterizes adult NSCs and their nichecell type-specific signatures and marker genes for 22 SVZ cell typesFree online tool to assess gene expression across 9,804 single cellscell type-specific dysfunctions underlying impaired adult neurogenesis

scholarly journals Astrocytic Propagation of Tau in the Context of Alzheimer's Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Rebecca M. Fleeman ◽  
Elizabeth A. Proctor
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Significance ◽  
Glial Cells ◽  
Cell Type ◽  
Tau Pathology ◽  
Specific Effects ◽  
Signaling Mechanisms ◽  
Cell Type Specific ◽  
The Brain

More than 6 million Americans are currently living with Alzheimer's disease (AD), and the incidence is growing rapidly with our aging population. Numerous therapeutics have failed to make it to the clinic, potentially due to a focus on presumptive pathogenic proteins instead of cell-type-specific signaling mechanisms. The tau propagation hypothesis that inter-neuronal tau transfer drives AD pathology has recently garnered attention, as accumulation of pathological tau in the brain has high clinical significance in correlating with progression of cognitive AD symptoms. However, studies on tau pathology in AD are classically neuron-centric and have greatly overlooked cell-type specific effects of tau internalization, degradation, and propagation. While the contribution of microglia to tau processing and propagation is beginning to be recognized and understood, astrocytes, glial cells in the brain important for maintaining neuronal metabolic, synaptic, trophic, and immune function which can produce, internalize, degrade, and propagate tau are understudied in their ability to affect AD progression through tau pathology. Here, we showcase evidence for whether tau uptake by astrocytes may be beneficial or detrimental to neuronal health and how astrocytes and their immunometabolic functions may be key targets for future successful AD therapies.

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