scholarly journals Transcription factors CTCF and Pax6 are segregated to different cell types during retinal cell differentiation

2008 ◽  
Vol 237 (3) ◽  
pp. 758-767 ◽  
Author(s):  
M. Valeria Canto-Soler ◽  
Hu Huang ◽  
M. Soledad Romero ◽  
Ruben Adler
Development ◽  
1979 ◽  
Vol 54 (1) ◽  
pp. 37-46
Author(s):  
L. Soriano ◽  
D. Paulin

Specific anti-DNase-I IgG have been used to detect deoxyribonuclease in teratocarcinoma cells by an indirect immunofluorescence method. All the cells studied show fluorescence staining. However, the patterns are quite different in embryonal carcinoma cells (amorphous cytoplasmic fluorescence and absence of nuclear staining) as compared to differentiated cell lines (diffuse, bright granular nuclear and fibrillar cytoplasmic fluorescence). It is possible by this method to distinguish different cell types derived from the same origin. Deoxyribonuclease from teratocarcinoma cells can therefore be considered as a marker of cell differentiation in this system.


2007 ◽  
Vol 24 (3) ◽  
pp. 409-421 ◽  
Author(s):  
BHAVANI KASHYAP ◽  
LOGAN C. FREDERICKSON ◽  
DEBORAH L. STENKAMP

The exposure of the developing human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the visual system. One common phenotype seen in humans exposed to ethanol in utero is microphthalmia. The objective of this study was to describe the effects of ethanol during retinal neurogenesis in a model organism, the zebrafish, and to pursue the potential mechanisms by which ethanol causes microphthalmia. Zebrafish embryos were exposed to 1% or 1.5% ethanol from 24 to 48 h after fertilization, a period during which the retinal neuroepithelium undergoes rapid proliferation and differentiation to form a laminated structure composed of different retinal cell types. Ethanol exposure resulted in significantly reduced eye size immediately following the treatment, and this microphthalmia persisted through larval development. This reduced eye size could not entirely be accounted for by the accompanying general delay in embryonic development. Retinal cell death was only slightly higher in ethanol-exposed embryos, although cell death in the lens was extensive in some of these embryos, and lenses were significantly reduced in size as compared to those of control embryos. The initiation of retinal neurogenesis was not affected, but the subsequent waves of cell differentiation were markedly reduced. Even cells that were likely generated after ethanol exposure—rod and cone photoreceptors and Müller glia—were delayed in their expression of cell-specific markers by at least 24 h. We conclude that ethanol exposure over the time of retinal neurogenesis resulted in persistent microphthalmia due to a combination of an overall developmental delay, lens abnormalities, and reduced retinal cell differentiation.


Author(s):  
Wenjun Yan ◽  
Mallory A. Laboulaye ◽  
Nicholas M. Tran ◽  
Irene E. Whitney ◽  
Inbal Benhar ◽  
...  

ABSTRACTAmacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion cells (RGCs), rendering each RGC type selectively sensitive to particular visual features, which are then relayed to the brain. While many AC types have been identified morphologically and physiologically, they have not been comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing (scRNA-seq) to profile >32,000 ACs from mouse retina, and applied computational methods to identify 63 AC types. We identified molecular markers for each type, and used them to characterize the morphology of multiple types. We show that they include nearly all previously known AC types as well as many that had not been described. Consistent with previous studies, most of the AC types express markers for the canonical inhibitory neurotransmitters GABA or glycine, but several express neither or both. In addition, many express one or more neuropeptides, and two express glutamatergic markers. We also explored transcriptomic relationships among AC types and identified transcription factors expressed by individual or multiple closely related types. Noteworthy among these were Meis2 and Tcf4, expressed by most GABAergic and most glycinergic types, respectively. Together, these results provide a foundation for developmental and functional studies of ACs, as well as means for genetically accessing them. Along with previous molecular, physiological and morphological analyses, they establish the existence of at least 130 neuronal types and nearly 140 cell types in mouse retina.SIGNIFICANCE STATEMENTThe mouse retina is a leading model for analyzing the development, structure, function and pathology of neural circuits. A complete molecular atlas of retinal cell types provides an important foundation for these studies. We used high-throughput single-cell RNA sequencing (scRNA-seq) to characterize the most heterogeneous class of retinal interneurons, amacrine cells, identifying 63 distinct types. The atlas includes types identified previously as well as many novel types. We provide evidence for use of multiple neurotransmitters and neuropeptides and identify transcription factors expressed by groups of closely related types. Combining these results with those obtained previously, we proposed that the mouse retina contains 130 neuronal types, and is therefore comparable in complexity to other regions of the brain.


2020 ◽  
Vol 21 (21) ◽  
pp. 8087
Author(s):  
Maxence Cornut ◽  
Emilie Bourdonnay ◽  
Thomas Henry

Inflammasomes are multimolecular complexes with potent inflammatory activity. As such, their activity is tightly regulated at the transcriptional and post-transcriptional levels. In this review, we present the transcriptional regulation of inflammasome genes from sensors (e.g., NLRP3) to substrates (e.g., IL-1β). Lineage-determining transcription factors shape inflammasome responses in different cell types with profound consequences on the responsiveness to inflammasome-activating stimuli. Pro-inflammatory signals (sterile or microbial) have a key transcriptional impact on inflammasome genes, which is largely mediated by NF-κB and that translates into higher antimicrobial immune responses. Furthermore, diverse intrinsic (e.g., circadian clock, metabolites) or extrinsic (e.g., xenobiotics) signals are integrated by signal-dependent transcription factors and chromatin structure changes to modulate transcriptionally inflammasome responses. Finally, anti-inflammatory signals (e.g., IL-10) counterbalance inflammasome genes induction to limit deleterious inflammation. Transcriptional regulations thus appear as the first line of inflammasome regulation to raise the defense level in front of stress and infections but also to limit excessive or chronic inflammation.


Author(s):  
Maxence Cornut ◽  
Emilie Bourdonnay ◽  
Thomas Henry

Inflammasomes are multimolecular complexes with potent inflammatory activity. As such, their activity is tightly regulated at the transcriptional and post-transcriptional levels. In this review, we present the transcriptional regulation of inflammasome genes from sensors (e.g NLRP3) to substrates (e.g. IL-1β). Lineage-determining transcription factors shape inflammasome responses in different cell types with profound consequences on the responsiveness to inflammasome-activating stimuli. Pro-inflammatory signals (sterile or microbial) have a key transcriptional impact on inflammasome genes, which is largely mediated by NF-κB and, that translates into higher antimicrobial immune responses. Furthermore, diverse intrinsic (e.g. circadian clock, metabolites) or extrinsic (e.g. xenobiotics) signals are integrated by signal-dependent transcription factors and chromatin structure changes to modulate transcriptionally inflammasome responses. Finally, anti-inflammatory signals (e.g. IL-10) counterbalance inflammasome genes induction to limit deleterious inflammation. Transcriptional regulations thus appear as the first line of inflammasome regulation to raise the defense level in front of stress and infections but also to limit excessive or chronic inflammation.


2021 ◽  
Vol 15 ◽  
Author(s):  
Mingchao Li ◽  
Qing Min ◽  
Matthew C. Banton ◽  
Xinpeng Dun

Advances in single-cell RNA sequencing technologies and bioinformatics methods allow for both the identification of cell types in a complex tissue and the large-scale gene expression profiling of various cell types in a mixture. In this report, we analyzed a single-cell RNA sequencing (scRNA-seq) dataset for the intact adult mouse sciatic nerve and examined cell-type specific transcription factor expression and activity during peripheral nerve homeostasis. In total, we identified 238 transcription factors expressed in nine different cell types of intact mouse sciatic nerve. Vascular smooth muscle cells have the lowest number of transcription factors expressed with 17 transcription factors identified. Myelinating Schwann cells (mSCs) have the highest number of transcription factors expressed, with 61 transcription factors identified. We created a cell-type specific expression map for the identified 238 transcription factors. Our results not only provide valuable information about the expression pattern of transcription factors in different cell types of adult peripheral nerves but also facilitate future studies to understand the function of key transcription factors in the peripheral nerve homeostasis and disease.


2002 ◽  
Vol 205 (17) ◽  
pp. 2583-2590
Author(s):  
Satoshi Sawai ◽  
Takashi Hirano ◽  
Yasuo Maeda ◽  
Yasuji Sawada

SUMMARYRecently it was demonstrated that a rapidly forming, self-organizing pattern that emerges within two-dimensional Dictyostelium discoideumcell cultures could later give rise to stripes of distinct zones, each comprising different cell types. Here we report physiological aspects of the initial rapid patterning and its relationship to cell differentiation. We found that as the temperature is lowered the characteristic length of the pattern increases. From this we estimated the activation energy of the patterning kinetics. Fluorescence of fluorescein-conjugated dextran revealed that the cytosolic pH of cells in the inside zone becomes lower than that in the outer zone facing the air. The patterning could be inhibited by addition of the plasma-membrane proton pump inhibitors diethystilbestrol (DES) or miconazole. Preincubation of cells with weak acid delayed the timing of the patterning, whereas weak base hastened it. A pH-indicating dye revealed localized accumulation of ammonia in the extracellular space. These results suggest that gradients of secreted metabolites may be directly responsible for the rapid patterning and its consequence on cell differentiation in a confined geometrical situation. Possible diffusible candidate molecules and a reaction scheme coupled to the imposed oxygen gradient are discussed.


Development ◽  
2020 ◽  
Vol 147 (14) ◽  
pp. dev187922 ◽  
Author(s):  
Candace S. Y. Chan ◽  
Nicolas Lonfat ◽  
Rong Zhao ◽  
Alexander E. Davis ◽  
Liang Li ◽  
...  

ABSTRACTTranscription factors (TFs) are often used repeatedly during development and homeostasis to control distinct processes in the same and/or different cellular contexts. Considering the limited number of TFs in the genome and the tremendous number of events that need to be regulated, re-use of TFs is necessary. We analyzed how the expression of the homeobox TF, orthodenticle homeobox 2 (Otx2), is regulated in a cell type- and stage-specific manner during development in the mouse retina. We identified seven Otx2 cis-regulatory modules (CRMs), among which the O5, O7 and O9 CRMs mark three distinct cellular contexts of Otx2 expression. We discovered that Otx2, Crx and Sox2, which are well-known TFs regulating retinal development, bind to and activate the O5, O7 or O9 CRMs, respectively. The chromatin status of these three CRMs was found to be distinct in vivo in different retinal cell types and at different stages. We conclude that retinal cells use a cohort of TFs with different expression patterns and multiple CRMs with different chromatin configurations to regulate the expression of Otx2 precisely.


2019 ◽  
Vol 48 (3) ◽  
pp. 1131-1145
Author(s):  
She Zhang ◽  
Fangyuan Chen ◽  
Ivet Bahar

Abstract Advances in chromosome conformation capture techniques as well as computational characterization of genomic loci structural dynamics open new opportunities for exploring the mechanistic aspects of genome-scale differences across different cell types. We examined here the dynamic basis of variabilities between different cell types by investigating their chromatin mobility profiles inferred from Hi-C data using an elastic network model representation of the chromatin. Our comparative analysis of sixteen cell lines reveals close similarities between chromosomal dynamics across different cell lines on a global scale, but notable cell-specific variations emerge in the detailed spatial mobilities of genomic loci. Closer examination reveals that the differences in spatial dynamics mainly originate from the difference in the frequencies of their intrinsically accessible modes of motion. Thus, even though the chromosomes of different types of cells have access to similar modes of collective movements, not all modes are deployed by all cells, such that the effective mobilities and cross-correlations of genomic loci are cell-type-specific. Comparison with RNA-seq expression data reveals a strong overlap between highly expressed genes and those distinguished by high mobilities in the present study, in support of the role of the intrinsic spatial dynamics of chromatin as a determinant of cell differentiation.


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