scholarly journals Cell Type-Selective Loss of Peroxisomal β-Oxidation Impairs Bipolar Cell but Not Photoreceptor Survival in the Retina

Cells ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 161
Author(s):  
Daniëlle Swinkels ◽  
Yannick Das ◽  
Sai Kocherlakota ◽  
Stefan Vinckier ◽  
Eric Wever ◽  
...  
Keyword(s):  
Bipolar Cell ◽  
Cell Types ◽  
Bipolar Cells ◽  
Cell Type ◽  
Peroxisomal Disorders ◽  
Multifunctional Protein ◽  
Ribbon Synapses ◽  
Different Cell Types ◽  
Oxidation Enzyme ◽  
Photoreceptor Death

Retinal degeneration is a common feature in peroxisomal disorders leading to blindness. Peroxisomes are present in the different cell types of the retina; however, their precise contribution to retinal integrity is still unclear. We previously showed that mice lacking the central peroxisomal β-oxidation enzyme, multifunctional protein 2 (MFP2), develop an early onset retinal decay including photoreceptor cell death. To decipher the function of peroxisomal β-oxidation in photoreceptors, we generated cell type selective Mfp2 knockout mice, using the Crx promotor targeting photoreceptors and bipolar cells. Surprisingly, Crx-Mfp2−/− mice maintained photoreceptor length and number until the age of 1 year. A negative electroretinogram was indicative of preserved photoreceptor phototransduction, but impaired downstream bipolar cell signaling from the age of 6 months. The photoreceptor ribbon synapse was affected, containing free-floating ribbons and vesicles with altered size and density. The bipolar cell interneurons sprouted into the ONL and died. Whereas docosahexaenoic acid levels were normal in the neural retina, levels of lipids containing very long chain polyunsaturated fatty acids were highly increased. Crx-Pex5−/− mice, in which all peroxisomal functions are inactivated in photoreceptors and bipolar cells, developed the same phenotype as Crx-Mfp2−/− mice. In conclusion, the early photoreceptor death in global Mfp2−/− mice is not driven cell autonomously. However, peroxisomal β-oxidation is essential for the integrity of photoreceptor ribbon synapses and of bipolar cells.

Unusual coupling patterns of a cone bipolar cell in the rabbit retina

1999 ◽  
Vol 16 (6) ◽  
pp. 1029-1035 ◽  
Author(s):  
STEPHEN L. MILLS
Keyword(s):  
Gap Junctions ◽  
Bipolar Cell ◽  
Plexiform Layer ◽  
Cell Types ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Rabbit Retina ◽  
Retinal Bipolar Cells ◽  
Different Cell Types ◽  
Cone Bipolar Cells

In mammals, gap junctions between retinal bipolar cells are generally small and tracer coupling has not been previously demonstrated. In this study, Neurobiotin was injected into the Ba3-type cone bipolar cell, a medium-field cone bipolar cell that ramifies in sublamina a of the rabbit retina. Tracer spread to many other Ba3 bipolar cells, presumably through gap junctions. It also spread to a smaller field bipolar cell called the Ba1 that ramifies at the same depth of the inner plexiform layer. Injection of Neurobiotin into Ba1 bipolar cells did not produce staining beyond the injected cell. Tracer coupling from the Ba3 was therefore both heterologous, in that different cell types were stained, and asymmetric. The unusual properties of this bipolar cell suggest that its function may differ from that of most cone bipolar cells, which are narrow-field, do not overlap, and are poorly coupled to one another.

Retinal bipolar cell types differ in their inventory of ion channels

2006 ◽  
Vol 23 (2) ◽  
pp. 143-154 ◽  
Author(s):  
ELENA IVANOVA ◽  
FRANK MÜLLER
Keyword(s):  
Patch Clamp ◽  
Bipolar Cell ◽  
Cell Types ◽  
Bipolar Cells ◽  
Hcn Channels ◽  
Hcn Channel ◽  
Cell Type ◽  
Morphological Classification ◽  
Voltage Gated ◽  
Channel Currents

Bipolar cells were recorded in rat retinal slices to study the distribution of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. Patch-clamp whole cell measurements were combined with intracellular filling and recorded cells were morphologically identified. HCN channel isoforms HCN1-4 are differentially expressed in bipolar cells. Each bipolar cell type has a characteristic inventory of HCN channels. The combination of HCN channel currents and other voltage-gated currents can be used as a kind of “finger print” to electrophysiologically identify and classify bipolar cell types. Using this approach of combined electrophysiological and morphological classification we could identify a new ON-cone bipolar cell type.

scholarly journals SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models

2020 ◽  
Author(s):  
Yupeng Wang ◽  
Rosario B. Jaime-Lara ◽  
Abhrarup Roy ◽  
Ying Sun ◽  
Xinyue Liu ◽  
...  
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Dna Sequences ◽  
Cell Types ◽  
Learning Models ◽  
Cell Type ◽  
Coding Sequences ◽  
Sequence Features ◽  
Cell Type Specific ◽  
Different Cell Types

AbstractWe propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of “strong enhancer” chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. For any DNA sequence, sequential k-mer (k=5, 7, 9 and 11) fold changes relative to randomly selected non-coding sequences were used as features for deep learning models. Three deep learning models were implemented, including multi-layer perceptron (MLP), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). All models in SeqEnhDL outperform state-of-the-art enhancer classifiers including gkm-SVM and DanQ, with regard to distinguishing cell type-specific enhancers from randomly selected non-coding sequences. Moreover, SeqEnhDL is able to directly discriminate enhancers from different cell types, which has not been achieved by other enhancer classifiers. Our analysis suggests that both enhancers and their tissue-specificity can be accurately identified according to their sequence features. SeqEnhDL is publicly available at https://github.com/wyp1125/SeqEnhDL.

Differential expression of glutamate receptor genes (GluR1-5) in the rat retina

1992 ◽  
Vol 8 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Thomas E. Hughes ◽  
Irm Hermans-Borgmeyer ◽  
Steve Heinemann
Keyword(s):  
Glutamate Receptor ◽  
Amacrine Cells ◽  
Cell Types ◽  
Bipolar Cells ◽  
Inner Nuclear Layer ◽  
Dissociated Cells ◽  
Different Cell Types ◽  
The Brain ◽  
Overlapping Sets

AbstractThe recent isolation of at least five different cDNAs encoding functional subunits of glutamate receptors (GluR1 to GluR5) has revealed a diversity whose function is not understood. To learn more about how these different receptor subunits are used in the brain, we undertook an in situ hybridization study of the retina to define how the different glutamate receptor genes are expressed. We chose the retina because the glutamate sensitivities of its different cell types have been characterized, and these different neurons reside in different laminae.Hybridization of [35S]UTP-labeled cRNA probes with transverse sections and freshly dissociated cells reveals that all five receptor subunits are expressed in the retina. Hybridization signal is detected in different, but overlapping, sets of cells in the retina. GluR1, GluR2, and GluR5 are expressed by many somata, and GluR4 by a few, in the outer third of the inner nuclear layer, where the horizontal cells reside. Transcripts for GluR1, GluR2, and GluR5 are found in the somata within the middle third of the inner nuclear layer, which is where the bipolar cell somata are located, and GluR2 probes label freshly dissociated rod bipolar cells. All of the probes produce labeling over the cells at the inner edge of the inner nuclear layer, which are probably amacrine cells, as well as over the cell bodies in the ganglion cell layer.

scholarly journals The complement of desmosomal plaque proteins in different cell types.

1985 ◽  
Vol 101 (4) ◽  
pp. 1442-1454 ◽  
Author(s):  
P Cowin ◽  
H P Kapprell ◽  
W W Franke
Keyword(s):  
Guinea Pig ◽  
Cell Types ◽  
Cardiac Cells ◽  
Myocardial Tissue ◽  
Cell Type ◽  
Wide Range ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific ◽  
Different Cell Types

Desmosomal plaque proteins have been identified in immunoblotting and immunolocalization experiments on a wide range of cell types from several species, using a panel of monoclonal murine antibodies to desmoplakins I and II and a guinea pig antiserum to desmosomal band 5 protein. Specifically, we have taken advantage of the fact that certain antibodies react with both desmoplakins I and II, whereas others react only with desmoplakin I, indicating that desmoplakin I contains unique regions not present on the closely related desmoplakin II. While some of these antibodies recognize epitopes conserved between chick and man, others display a narrow species specificity. The results show that proteins whose size, charge, and biochemical behavior are very similar to those of desmoplakin I and band 5 protein of cow snout epidermis are present in all desmosomes examined. These include examples of simple and pseudostratified epithelia and myocardial tissue, in addition to those of stratified epithelia. In contrast, in immunoblotting experiments, we have detected desmoplakin II only among cells of stratified and pseudostratified epithelial tissues. This suggests that the desmosomal plaque structure varies in its complement of polypeptides in a cell-type specific manner. We conclude that the obligatory desmosomal plaque proteins, desmoplakin I and band 5 protein, are expressed in a coordinate fashion but independently from other differentiation programs of expression such as those specific for either epithelial or cardiac cells.

scholarly journals Distribution and modulation of the cellular receptor for transforming growth factor-beta.

1987 ◽  
Vol 105 (2) ◽  
pp. 965-975 ◽  
Author(s):  
L M Wakefield ◽  
D M Smith ◽  
T Masui ◽  
C C Harris ◽  
M B Sporn
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Tgf Beta ◽  
Cell Type ◽  
Down Regulation ◽  
Growth Factor Beta ◽  
Different Cell Types

Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF-beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF-beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down-regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus.

scholarly journals Characterization of a novel large-field cone bipolar cell type in the primate retina: Evidence for selective cone connections

2010 ◽  
Vol 28 (1) ◽  
pp. 29-37 ◽  
Author(s):  
HANNAH R. JOO ◽  
BETH B. PETERSON ◽  
TONI J. HAUN ◽  
DENNIS M. DACEY
Keyword(s):  
Giant Cell ◽  
Bipolar Cell ◽  
Visual Information ◽  
Dendritic Tree ◽  
Cell Types ◽  
Giant Cells ◽  
Bipolar Cells ◽  
Large Field ◽  
Inner Plexiform Layer ◽  
Dendritic Field

AbstractParallel processing of visual information begins at the first synapse in the retina between the photoreceptors and bipolar cells. Ten bipolar cell types have been previously described in the primate retina: one rod and nine cone bipolar types. In this paper, we describe an 11th type of bipolar cell identified in Golgi-stained macaque retinal whole mount and vertical section. Axonal stratification depth, in addition to dendritic and axonal morphology, distinguished the “giant” cell from all previously well-recognized bipolar cell types. The giant bipolar cell had a very large and sparsely branched dendritic tree and a relatively large axonal arbor that costratified with the DB4 bipolar cell near the center of the inner plexiform layer. The sparseness of the giant bipolar’s dendritic arbor indicates that, like the blue cone bipolar, it does not contact all the cones in its dendritic field. Giant cells contacting the same cones as midget bipolar cells, which are known to contact single long-wavelength (L) or medium-wavelength (M) cones, demonstrate that the giant cell does not exclusively contact short-wavelength (S) cones and, therefore, is not a variant of the previously described blue cone bipolar. This conclusion is further supported by measurement of the cone contact spacing for the giant bipolar. The giant cell contacts an average of about half the cones in its dendritic field (mean ± s.d. = 52 ± 17.6%; n = 6), with a range of 27–82%. The dendrites from single or neighboring giant cells that converge onto the same cones suggest that the giant cell may selectively target a subset of cones with a highly variable local density, such as the L or M cones.

scholarly journals Detection of cell-type-specific risk-CpG sites in epigenome-wide association studies

2018 ◽  
Author(s):  
Xiangyu Luo ◽  
Can Yang ◽  
Yingying Wei
Keyword(s):  
High Resolution ◽  
Statistical Method ◽  
Individual Cell ◽  
Association Studies ◽  
Cell Types ◽  
Cell Type ◽  
Cpg Sites ◽  
Cpg Site ◽  
Cell Type Specific ◽  
Different Cell Types

In epigenome-wide association studies, the measured signals for each sample are a mixture of methylation profiles from different cell types. The current approaches to the association detection only claim whether a cytosine-phosphate-guanine (CpG) site is associated with the phenotype or not, but they cannot determine the cell type in which the risk-CpG site is affected by the phenotype. Here, we propose a solid statistical method, HIgh REsolution (HIRE), which not only substantially improves the power of association detection at the aggregated level as compared to the existing methods but also enables the detection of risk-CpG sites for individual cell types.

scholarly journals accuEnhancer: Accurate enhancer prediction by integration of multiple cell type data with deep learning

2020 ◽  
Author(s):  
Yi-An Tung ◽  
Wen-Tse Yang ◽  
Tsung-Ting Hsieh ◽  
Yu-Chuan Chang ◽  
June-Tai Wu ◽  
...  
Keyword(s):  
Deep Learning ◽  
Cell Types ◽  
Regulatory Elements ◽  
Sequence Motifs ◽  
Cell Type ◽  
Enhancer Activity ◽  
Multiple Cell ◽  
Type Data ◽  
Different Cell Types ◽  
Multiple Cell Type

AbstractEnhancers are one class of the regulatory elements that have been shown to act as key components to assist promoters in modulating the gene expression in living cells. At present, the number of enhancers as well as their activities in different cell types are still largely unclear. Previous studies have shown that enhancer activities are associated with various functional data, such as histone modifications, sequence motifs, and chromatin accessibilities. In this study, we utilized DNase data to build a deep learning model for predicting the H3K27ac peaks as the active enhancers in a target cell type. We propose joint training of multiple cell types to boost the model performance in predicting the enhancer activities of an unstudied cell type. The results demonstrated that by incorporating more datasets across different cell types, the complex regulatory patterns could be captured by deep learning models and the prediction accuracy can be largely improved. The analyses conducted in this study demonstrated that the cell type-specific enhancer activity can be predicted by joint learning of multiple cell type data using only DNase data and the primitive sequences as the input features. This reveals the importance of cross-cell type learning, and the constructed model can be applied to investigate potential active enhancers of a novel cell type which does not have the H3K27ac modification data yet.AvailabilityThe accuEnhancer package can be freely accessed at: https://github.com/callsobing/accuEnhancer

Colour receptors, and their synaptic connexions, in the retina of a cyprinid fish

1975 ◽  
Vol 270 (902) ◽  
pp. 61-118 ◽  
Keyword(s):  
Bipolar Cell ◽  
Cell Types ◽  
Bipolar Cells ◽  
Synaptic Terminals ◽  
Cone Type ◽  
Cone Cells ◽  
Sparse Population ◽  
Microscopic Morphology ◽  
The Individual ◽  
Dendritic Fields

Morphologically speaking, there are five kinds of cone cells in the retina of the rudd ( Scardinius erythrophthalmus ). But two of them, the principal elements of the double cones and the free principal cones, are probably functionally equivalent, while another, sparse, population of small ( oblique ) cones (which disappear in older fish), is unlikely to make a significant contribution to visual spectral sensitivity. Thus, principal and accessory cones (usually paired with one another), and single cones seem to be the three receptors which underlie the fish’s trichromacy. Photographic densitometry of individual cone cells was used to provide evidence that accessory cones contain a green-absorbing photopigment and the single cones a blue one. Other arguments are given in support of those identifications, and they also strongly suggest that principal cones contain the red-absorbing pigment. Golgi-impregnated bipolar cells were examined electron-microscopically to determine the specific patterns of synaptic connexion they make with these different, anatomically identifiable, colour cones and with the retinal rods. Three principal arrangements were distinguished (see figure 69, page 190). (1) Rod bipolar cells comprise two distinct morphological types, both of which connect exclusively to principal (red) cones as well as to the rods within the outlines of their dendritic fields. (2) Selective cone bipolar cells, more delicate neurons with considerably wider dendritic fields, connect (according to type) to one or other of the different colour cone populations. Examples analysed were specific for the accessory (green) or for the single (blue) cones; no bipolar cells were found connected only to red cones. (3) Mixed cone bipolars have the smallest dendritic fields, and connect to combinations of cones (for example, red and green, or green and blue, but not red and blue). They also have synaptic input (usually relatively sparse) from the rods. Cells were encountered connecting to all three cone types, but they were only partially analysed, and are not described at length. The light microscopic morphology of these bipolar cell types consistently reflects the detailed pattern of connexion each makes with the different receptor populations (just as the morphology of the cones reflects the spectral properties of their photopigment). But while their synaptic connectivity is generally highly specific for cone type, they do occasionally make anomalous connexions with the ‘wrong’ receptors. There is a high degree of divergence (page 85) at the receptor-bipolar synapses, and the different kinds of cones each characteristically connect to different numbers of bipolar cells. Principal (red) cones, which are the most numerous, individually connect to more bipolars than cones of other types, whose characteristic synaptic divergence is likewise related to the frequency with which they occur in the retina. However, rods, which are much more numerous than cones, do not conform with this generalization. The selectivity with which the synaptic terminals of the different cones are connected together by their invaginating basal processes was also examined. These processes link neighbouring synaptic terminals of differently coloured cones: specifically, principal (red) cone basal processes invaginate accessory (green) cone pedicles, and vice versa. Single (blue) cone basal processes connect only to accessory cone pedicles, but that synaptic relation is not reciprocated. These synapses between the cones have important bearing upon interpretation of the bipolar cell connectivity patterns. In their light, the interaction between colour channels which the convergence of different cones onto the mixed cone bipolar dendrites mediates, seems to re-iterate a process already undertaken more peripherally. Likewise, whereas the anatomy of the selective cone bipolars appears designed to convey activity from the individual cone populations, the responses of the receptors they sample must already be influenced by activity in other colour channels.

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