A single-cell atlas of chromatin accessibility in the human genome

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Single-cell chromatin accessibility identifies enhancer networks driving gene expression during spinal cord development in mouse

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Structural and immunohistological modifications in olfactory bulb of the staggerer mutant mouse.

In the present study, we describe the structural and cytological changes observed in staggerer mutant olfactory bulbs, as compared to normal mice. On the basis of photonic and ultrastructural observations we tried to define the alterations induced by the mutation: i.e. a reduction of bulb size, a reduction in the volume of three out of the six architectonic layers (glomerular, external and internal plexiform), a reduction of glomeruli size, a loss of half the mitral cells and a slight decrease in juxtaglomerular interneuron number. In staggerer, an hypertrophy of glial ensheathing cell processes was especially evident at the level of each glomerulus, whereas the density of the astrocyte network was weaker in the granular layer and the nerve layer not apparently impaired. An immunofluorescent labelling study combined with confocal scanning microscopy was performed in order to identify the cellular type and the differentiation degree of the various elements. Antibodies anti-GFAP, a protein present in both ensheathing cells and astrocytes, and anti-OMP, the specific maturation protein of the nerve layer, were used for that purpose. Data confirmed the reality of the gliosis and the persistence of the sensory component in the mutant. All the structural alterations described in staggerer olfactory bulb were in close agreement with the functional troubles previously recorded. Our results are discussed in connection with the present knowledge on embryonal origin, fetal development and adult cellular renewal of the olfactory bulb.     

Postnatal developmental expression of calbindin, calretinin and parvalbumin in mouse main olfactory bulb

The distribution of calbindin, calretinin and parvalbumin during the development of the mouse main olfactory bulb (MOB) was studied using immunohistochemistry techniques. The results are as follows:(1) calbindin-immunoreactive profiles were mainly located in the glomerular layer, and few large calbindin-immunoreactive cells were found in the subependymal layer of postnatal day 10 (P10) to postnatal day 40 (P40) mice; (2) no calbindin was detected in the mitral cell layer at any stage; (3) calretinin-immunoreactive profiles were present in all layers of the main olfactory bulb at all stages, especially in the olfactory nerve layer, glomerular layer and granule cell layer; (4) parvalbumin-immunoreactive profiles were mainly located in the external plexiform layer (except for P10 mice); (5) weakly stained parvalbumin-immunoreactive profiles were present in the glomerular layer at all stages; and (6) no parvalbumin was detected in the mitral cell layer at any stage.     

Functional regeneration of the olfactory bulb requires reconnection to the olfactory nerve in Xenopus larvae

Larvae of the South African clawed frog (Xenopus laevis) can regenerate the telencephalon, which consists of the olfactory bulb and the cerebrum, after it has been partially removed. Some authors have argued that the telencephalon, once removed, must be reconnected to the olfactory nerve in order to regenerate. However, considerable regeneration has been observed before reconnection. Therefore, we have conducted several experiments to learn whether or not reconnection is a prerequisite for regeneration. We found that the olfactory bulb did not regenerate without reconnection, while the cerebrum regenerated by itself. On the other hand, when the brain was reconnected by the olfactory nerve, both the cerebrum and the olfactory bulb regenerated. Morphological and histological investigation showed that the regenerated telencephalon was identical to the intact one in morphology, types and distributions of cells, and connections between neurons. Froglets with a regenerated telencephalon also recovered olfaction, the primary function of the frog telencephalon. These results suggest that the Xenopus larva requires reconnection of the regenerating brain to the olfactory nerve in order to regenerate the olfactory bulb, and thus the regenerated brain functions, in order to process olfactory information.     

The somatotopic organization of the olfactory bulb in elasmobranchs

The olfactory bulbs (OBs) are bilaterally paired structures in the vertebrate forebrain that receive and process odor information from the olfactory receptor neurons (ORNs) in the periphery. Virtually all vertebrate OBs are arranged chemotopically, with different regions of the OB processing different types of odorants. However, there is some evidence that elasmobranch fishes (sharks, rays, and skates) may possess a gross somatotopic organization instead. To test this hypothesis, we used histological staining and retrograde tracing techniques to examine the morphology and organization of ORN projections from the olfactory epithelium (OE) to the OB in three elasmobranch species with varying OB morphologies. In all three species, glomeruli in the OB received projections from ORNs located on only the three to five lamellae situated immediately anterior within the OE. These results support that the gross arrangement of the elasmobranch OB is somatotopic, an organization unique among fishes and most other vertebrates. In addition, certain elasmobranch species possess a unique OB morphology in which each OB is physically subdivided into two or more “hemi‐olfactory bulbs.” Somatotopy could provide a preadaptation which facilitated the evolution of olfactory hemibulbs in these species. J. Morphol., 2013. © 2012 Wiley Periodicals, Inc.     

Comparison of social interaction and neural activation in the main olfactory bulb and the accessory olfactory bulb between Microtus mandarinus and Microtus fortis

To gain insight into the function of AOB and MOB during different social interaction and in different vole species,the behaviors and neural activation of the olfactory bulbs in social interactions of mandarin voles Microtus mandarinus and reed voles Microtus fortis were compared in the present research.Mandarin voles spent significantly more time attacking and sniffing their opponents and sniffing sawdust than reed voles.During same sex encounters,mandarin voles attacked their opponents for a significantly ...     

Unbiased chromatin accessibility profiling by RED-seq uncovers unique features of nucleosome variants in vivo

Background

Differential accessibility of DNA to nuclear proteins underlies the regulation of numerous cellular processes. Although DNA accessibility is primarily determined by the presence or absence of nucleosomes, differences in nucleosome composition or dynamics may also regulate accessibility. Methods for mapping nucleosome positions and occupancies genome-wide (MNase-seq) have uncovered the nucleosome landscapes of many different cell types and organisms. Conversely, methods specialized for the detection of large nucleosome-free regions of chromatin (DNase-seq, FAIRE-seq) have uncovered numerous gene regulatory elements. However, these methods are less successful in measuring the accessibility of DNA sequences within nucelosome arrays.

Results

Here we probe the genome-wide accessibility of multiple cell types in an unbiased manner using restriction endonuclease digestion of chromatin coupled to deep sequencing (RED-seq). Using this method, we identified differences in chromatin accessibility between populations of cells, not only in nucleosome-depleted regions of the genome (e.g., enhancers and promoters), but also within the majority of the genome that is packaged into nucleosome arrays. Furthermore, we identified both large differences in chromatin accessibility in distinct cell lineages and subtle but significant changes during differentiation of mouse embryonic stem cells (ESCs). Most significantly, using RED-seq, we identified differences in accessibility among nucleosomes harboring well-studied histone variants, and show that these differences depend on factors required for their deposition.

Conclusions

Using an unbiased method to probe chromatin accessibility genome-wide, we uncover unique features of chromatin structure that are not observed using more widely-utilized methods. We demonstrate that different types of nucleosomes within mammalian cells exhibit different degrees of accessibility. These findings provide significant insight into the regulation of DNA accessibility.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1104) contains supplementary material, which is available to authorized users.     

Function of attention in learning process in the olfactory bulb

It has been suggested that in the olfactory bulb, odor information is processed through parallel channels and learning depends on the cognitive environment. The synapse’s spike effective time is defined as the effective time for a spike from pre-synapse to post-synapse, which varies with the type of synapse. A learning model of the olfactory bulb was constructed for synapses with varying spike effective times. The simulation results showed that such a model can realize the multi-channel processing of information in the bulb. Furthermore, the effect of the cognitive environment on the learning process was also studied. Different feedback frequencies were used to express different attention states. Considering the information’s multi-channel processing requirement for learning, a learning rule considering both spike timing and average spike frequency is proposed. Simulation results showed that habituation and anti-habituation of an odor in the olfactory bulb might be the result of learning guided by a common local learning rule but at different attention states.     

Differentiation of human olfactory system-derived stem cells into dopaminergic neuron-like cells: A comparison between olfactory bulb and mucosa as two sources of stem cells

Cell transplantation has become a possible therapeutic approach in the treatment of neurodegenerative diseases of the nervous system by replacing lost cells. The current study aimed to make a comparison between the differentiation capacity of the olfactory bulb neural stem cells (OB-NSCs) and olfactory ectomesenchymal stem cells (OE-MSCs) into dopaminergic-like neurons under the inductive effect of transforming growth factor β (TGF-β). After culturing and treating with TGF-β, the differentiation capacities of both types of stem cells into dopaminergic neuron-like cells were evaluated. Quantitative real-time polymerase chain reaction analysis 3 weeks after induction demonstrated that the mRNA expression of the dopaminergic activity markers tyrosine hydroxylase (TH), dopamine transporter (DAT), paired box gene 2 (PAX2), and PAX5 in the neuron-like cells derived from OB-NSCs was significantly higher than those derived from OE-MSCs. These findings were further supported by the immunocytochemistry staining showing that the expression of the tyrosine hydroxylase, DAT, PAX2, and paired like homeodomain 3 seemed to be slightly higher in OB-NSCs compared with OE-MSCs. Despite the lower differentiation capacity of OE-MSCs, other considerations such as a noninvasive and easier harvesting process, faster proliferation attributes, longer life span, autologous transplantability, and also the easier and inexpensive cultural process of the OE-MSCs, cumulatively make these cells the more appropriate alternative in the case of autologous transplantation during the treatment process of neurodegenerative disorders like Parkinson's disease.     

Function of attention in learning process in the olfactory bulb

Biological experiments[1—8] have shown that in the olfactory bulb, odor information is encoded into spatio-temporal patterns and processed in multi-channels. In the bulb, the information is divided into basic information and fine information, which are encoded into average spiking frequency (long-term pattern) and synchronization of spikes[1—8] respectively. Compared with other structures in which information is encoded into spatio-temporal patterns, the olfactory bulb抯 structure is rather …     

Expression of EGR-1 in a subset of olfactory bulb dopaminergic cells

In the adrenal medulla, binding of the immediate early gene (IEG) proteins, EGR-1 (ZIF-268/KROX-24/NGFI-A) and AP-1, to the tyrosine hydroxylase (Th) proximal promoter mediate inducible Th expression. The current study investigated the potential role of EGR-1 in inducible Th expression in the olfactory bulb (OB) since IEGs bound to the AP-1 site in the Th proximal promoter are also necessary for activity-dependent OB TH expression. Immunohistochemical analysis of a naris-occluded mouse model of odor deprivation revealed weak EGR-1 expression levels in the OB glomerular layer that were activity-dependent. Immunofluorescence analysis indicated that a majority of glomerular cells expressing EGR-1 also co-expressed TH, but only small subset of TH-expressing cells contained EGR-1. By contrast, granule cells, which lack TH, exhibited EGR-1 expression levels that were unchanged by naris closure. Together, these finding suggest that EGR-1 mediates activity-dependent TH expression in a subset of OB dopaminergic neurons, and that there is differential regulation of EGR-1 in periglomerular and granule cells.     

A multi-omic single-cell landscape of human gynecologic malignancies

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A TAP1 null mutation leads to an enlarged olfactory bulb and supernumerary,ectopic olfactory glomeruli

Major histocompatibility class I (MHCI) molecules are well known for their immunological role in mediating tissue graft rejection. Recently, these molecules were discovered to be expressed in distinct neuronal subclasses, dispelling the long-held tenet that the uninjured brain is immune-privileged. Here, we show that MHCI molecules are expressed in the main olfactory bulb (MOB) of adult animals. Furthermore, we find that mice with diminished levels of MHCI expression have enlarged MOBs containing an increased number of small, morphologically abnormal and ectopically located P2 glomeruli. These findings suggest that MHCI molecules may play an important role in the proper formation of glomeruli in the bulb.     

Investigation of the role of interneurons and their modulation by centrifugal fibers in a neural model of the olfactory bulb

Olfactory bulb processing results from the interaction of relay neurons with two main categories of interneurons which mediate inhibition in two distinct layers: periglomerular cells and granule cells. We present here a neural model of the mammalian olfactory bulb which allows to separately investigate the functional consequences of the two types of interneurons onto the relay neurons responsiveness to odors. The model, although built with simplified representations of neural elements generates various aspects of neural dynamics from the cellular to the populational level. We propose that the combined action of centrifugal control at two different layers of processing is complementary: reduction of the number of active relay neurons responding to a given odorant through increased activity of periglomerular cells, and an increase of response intensity of active mitral cells through decrease of granule cell inhibition.     

Effects of in utero odorant exposure on neuroanatomical development of the olfactory bulb and odour preferences

Human babies and other young mammals prefer food odours and flavours of their mother's diet during pregnancy as well as their mother's individually distinctive odour. Newborn mice also prefer the individual odours of more closely related--even unfamiliar--lactating females. If exposure to in utero odorants-which include metabolites from the mother's diet and the foetus's genetically determined individual odour-helps shape the neuroanatomical development of the olfactory bulb, this could influence the perception of such biologically important odours that are preferred after birth. We exposed gene-targeted mice during gestation and nursing to odorants that activate GFP-tagged olfactory receptors (ORs) and then measured the effects on the size of tagged glomeruli in the olfactory bulb where axons from olfactory sensory neurons (OSNs) coalesce by OR type. We found significantly larger tagged glomeruli in mice exposed to these activating odorants in amniotic fluid, and later in mother's milk, as well as significant preferences for the activating odour. Larger glomeruli comprising OSNs that respond to consistently encountered odorants should enhance detection and discrimination of these subsequently preferred odours, which in nature would facilitate selection of palatable foods and kin recognition, through similarities in individual odours of relatives.     

Polysialic acid controls NCAM-induced differentiation of neuronal precursors into calretinin-positive olfactory bulb interneurons

Understanding the mechanisms that regulate neurogenesis is a prerequisite for brain repair approaches based on neuronal precursor cells. One important regulator of postnatal neurogenesis is polysialic acid (polySia), a post-translational modification of the neural cell adhesion molecule NCAM. In the present study, we investigated the role of polySia in differentiation of neuronal precursors isolated from the subventricular zone of early postnatal mice. Removal of polySia promoted neurite induction and selectively enhanced maturation into a calretinin-positive phenotype. Expression of calbindin and Pax6, indicative for other lineages of olfactory bulb interneurons, were not affected. A decrease in the number of TUNEL-positive cells indicated that cell survival was slightly improved by removing polySia. Time lapse imaging revealed the absence of chain migration and low cell motility, in the presence and absence of polySia. The changes in survival and differentiation, therefore, could be dissected from the well-known function of polySia as a promoter of precursor migration. The differentiation response was mimicked by exposure of cells to soluble or substrate-bound NCAM and prevented by the C3d-peptide, a synthetic ligand blocking NCAM interactions. Moreover, a higher degree of differentiation was observed in cultures from polysialyltransferase-depleted mice and after NCAM exposure of precursors from NCAM-knockout mice demonstrating that the NCAM function is mediated via heterophilic binding partners. In conclusion, these data reveal that polySia controls instructive NCAM signals, which direct the differentiation of subventricular zone-derived precursors towards the calretinin-positive phenotype of olfactory bulb interneurons.