scholarly journals Ectopic synthesis of epidermal cytokeratins in pancreatic islet cells of transgenic mice interferes with cytoskeletal order and insulin production.

1993 ◽  
Vol 120 (3) ◽  
pp. 743-755 ◽  
Author(s):  
M Blessing ◽  
U Rüther ◽  
W W Franke
Keyword(s):  
Transgenic Mice ◽  
Beta Cells ◽  
Cell Function ◽  
Cultured Cells ◽  
Ectopic Expression ◽  
Epidermal Keratinocytes ◽  
Cell Type ◽  
Cell Functions ◽  
Insulin Promoter ◽  
Cell Type Specific

The members of the multigene family of intermediate filament (IF) proteins are expressed in various combinations and amounts that are specific for a given pathway or state of differentiation. Previous experiments in which the cell type-specific IF cytoskeleton was altered by introducing foreign IF proteins into cultured cells or certain tissues of transgenic animals have shown a remarkable tolerance, without detectable interference with cell functions. To examine the importance of the cell type-specific cytokeratin (CK) IF pattern, we have studied the ectopic expression of CK genes in different epithelia of transgenic mice. Here we report changes observed in the beta cells of pancreatic islets expressing the genes for human epidermal CKs 1 and/or 10 brought under control of the rat insulin promoter. Both genes were efficiently expressed, resulting in the appearance of numerous and massive bundles of aggregated IFs, resembling those of epidermal keratinocytes. While the synthesis of epidermal CK 10 was readily accommodated and compatible with cell function, mice expressing CK 1 in their beta cells, alone or in combination with CK 10, developed a special form of diabetes characterized by a drastic reduction of insulin-secretory vesicles and of insulin-and CK 1-producing cells. In many CK 1-producing cells, accumulations of fibrous or granular material containing CK 1 were also seen in the nucleus. This demonstration of functional importance of the specific CK-complement in an epithelial cell indicates a contribution of cell type-specific factors to cytoplasmic IF compartmentalization and that the specific CK complement can be crucial for functions and longevity of a given kind of epithelium.

Downregulation of renal TonEBP in hypokalemic rats

2007 ◽  
Vol 293 (1) ◽  
pp. F408-F415 ◽  
Author(s):  
Un Sil Jeon ◽  
Ki-Hwan Han ◽  
Soo-Hyun Park ◽  
Sang Do Lee ◽  
Mee Rie Sheen ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Renal Medulla ◽  
Distal Tubule ◽  
Cell Type ◽  
Outer Medulla ◽  
Sodium Transporters ◽  
Enhancer Binding Protein ◽  
Collecting Ducts ◽  
Cell Type Specific ◽  
Underlying Mechanisms

Hypokalemia causes a significant decrease in the tonicity of the renal medullary interstitium in association with reduced expression of sodium transporters in the distal tubule. We asked whether hypokalemia caused downregulation of the tonicity-responsive enhancer binding protein (TonEBP) transcriptional activator in the renal medulla due to the reduced tonicity. We found that the abundance of TonEBP decreased significantly in the outer and inner medullas of hypokalemic rats. Underlying mechanisms appeared different in the two regions because the abundance of TonEBP mRNA was lower in the outer medulla but unchanged in the inner medulla. Immunohistochemical examination of TonEBP revealed cell type-specific differences. TonEBP expression decreased dramatically in the outer and inner medullary collecting ducts, thick ascending limbs, and interstitial cells. In the descending and ascending thin limbs, TonEBP abundance decreased modestly. In the outer medulla, TonEBP shifted to the cytoplasm in the descending thin limbs. As expected, transcription of aldose reductase, a target of TonEBP, was decreased since the abundance of mRNA and protein was reduced. Downregulation of TonEBP appeared to have also contributed to reduced expression of aquaporin-2 and UT-A urea transporters in the renal medulla. In cultured cells, expression and activity of TonEBP were not affected by reduced potassium concentrations in the medium. These data support the view that medullary tonicity regulates expression and nuclear distribution of TonEBP in the renal medulla in cell type-specific manners.

Cell-Type-Specific Expression of a TESK1 Promoter-Linked lacZ Gene in Transgenic Mice

2001 ◽  
Vol 286 (3) ◽  
pp. 566-573 ◽  
Author(s):  
Jiro Toshima ◽  
Junko Y. Toshima ◽  
Misao Suzuki ◽  
Tetsuo Noda ◽  
Kensaku Mizuno
Keyword(s):  
Transgenic Mice ◽  
Lacz Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

scholarly journals Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes

Blood ◽  
2014 ◽  
Vol 124 (25) ◽  
pp. 3719-3729 ◽  
Author(s):  
Jason S. Weinstein ◽  
Kimberly Lezon-Geyda ◽  
Yelena Maksimova ◽  
Samuel Craft ◽  
Yaoping Zhang ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Cell Function ◽  
Cell Type ◽  
Effector Cells ◽  
T Effector Cells ◽  
Follicular Helper ◽  
Key Points ◽  
Cell Type Specific ◽  
Global Transcriptome

Key Points Transcriptomes and enhancers of human CD4+ Tfh and non-Tfh T effector cells reveal cell type–specific differences. These data are a significant resource for understanding mechanisms of normal and perturbed Tfh cell function.

scholarly journals c-maf Promotes T Helper Cell Type 2 (Th2) and Attenuates Th1 Differentiation by Both Interleukin 4–dependent and –independent Mechanisms

1998 ◽  
Vol 188 (10) ◽  
pp. 1859-1866 ◽  
Author(s):  
I-Cheng Ho ◽  
David Lo ◽  
Laurie H. Glimcher
Keyword(s):  
Transgenic Mice ◽  
Ectopic Expression ◽  
T Helper Cell ◽  
Helper Cell ◽  
Th2 Cytokines ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type

The c-maf protooncogene is a T helper cell type 2 (Th2)-specific transcription factor that activates the interleukin (IL)-4 promoter in vitro. Although it has been postulated that c-maf directs the Th2-specific expression of the IL-4 gene in vivo, direct evidence that c-maf functions during the differentiation of normal, primary T cells is lacking. We now demonstrate that overexpression of c-maf in vivo skews the Th immune response along a Th2 pathway, as evidenced by increased production of Th2 cytokines and the IL-4–dependent immunoglobulins, IgG1 and IgE. The overproduction of IgGl and IgE in the CD4 promoter/c-maf transgenic mice was IL-4 dependent since this was not observed in c-maf transgenic mice bred onto an IL-4–deficient background. Ectopic expression of c-maf in mature Th1 cells did not confer on them the ability to produce IL-4, but did decrease the production of IFN-γ. The attenuation of Th1 differentiation by c-maf overexpression occurred by a mechanism that was independent of IL-4 and other Th2 cytokines, and could be overcome by IL-12. These studies demonstrate that c-maf promotes Th2 differentiation by IL-4–dependent mechanisms and attenuates Th1 differentiation by Th2 cytokine-independent mechanisms.

scholarly journals Cell type specific accumulation of the major latency-associated transcript (LAT) of herpes simplex virus type 2 in LAT transgenic mice

Virology ◽  
2009 ◽  
Vol 386 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Kening Wang ◽  
Gowtham Mahalingam ◽  
Yumi Imai ◽  
Lesley Pesnicak ◽  
Todd T. Margolis ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Transgenic Mice ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Cell Type ◽  
Specific Accumulation ◽  
Cell Type Specific ◽  
Simplex Virus

scholarly journals P004 Critical paralog proteins has a cell-type specific rewiring role in Ulcerative Colitis associated signalling processes

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S126-S127
Author(s):  
P Kornilova ◽  
L Potari-Gul ◽  
D Modos ◽  
M Madgwick ◽  
W Haerty ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Notch Pathway ◽  
Cell Types ◽  
Goblet Cells ◽  
Signalling Pathways ◽  
Cell Type ◽  
Altered Expression ◽  
Hypoxia Response ◽  
Cell Functions ◽  
Cell Type Specific

Abstract Background Cell functions are regulated by signalling pathways that often cross-talk with each other. These cross-talks are usually cell-type specific and, as we showed earlier, often mediated by so called critical paralog proteins (proteins resulted due to gene duplication but then diverged both in terms of their regulation and their functions). As dysregulation of cell functions is a hallmark of chronic inflammatory diseases, including Ulcerative Colitis (UC), here we investigated the role of such critical paralog proteins in the regulation of some key functions, in UC-associated cell types. Methods In this study, we compared healthy and diseased (non-inflamed UC) conditions. Using network biology approaches combined with single-cell RNAseq data, we identified critical paralog groups in myofibroblasts, regulatory T cells and goblet cells that show cell and/or condition specificity in the process of autophagy, Notch and T-cell receptor signalling. Results We focused our analysis on the Notch pathway-related processes, in particular the EGLN paralogs (EGLN1-3). The EGLN enzymes are prolyl hydroxylases and EGLN1, EGLN3 can directly inhibit the HIF1A transcription factor, while HIF1A induces the expression of all the three EGLN gene upon hypoxia. This negative feedback loop tends to control the amount of EGLNs and the activation status of the HIF1A proteins, therefore maintaining an adequate hypoxia response. In the intestine, EGLN2 and EGLN3 are described as potential regulators of inflammation, and both are downregulated in UC patients. Importantly, we found that the expression of EGLN paralogs shows cell-type and condition specificity. While goblet cells express all three paralogs in both healthy and UC conditions, myofibroblasts express EGLN3 only in the healthy condition. As EGLN3 is responsible for tight junction integrity, and it can regulate hypoxia response, the lack of EGLN3 in UC could contribute to the disrupted epithelial barrier function and dysregulation of myofibroblasts. Accordingly, in mice, depletion of Egln3 causes an increased susceptibility to colitis. Conclusion We have developed a bioinformatic pipeline to reconstruct cell-type specific signalling networks to identify the key differences among critical regulators of the signalling flow (ie., critical paralog proteins) in UC-associated cell types and in comparison of healthy and non-inflamed UC conditions. We analysed the altered expression of paralog genes in signalling pathways in UC-associated cell-types, and demonstrated their role with the condition and cell-type specific expression of EGLN3.

scholarly journals A cis-regulatory atlas in maize at single-cell resolution

2020 ◽  
Author(s):  
Alexandre P. Marand ◽  
Zongliang Chen ◽  
Andrea Gallavotti ◽  
Robert J. Schmitz
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cellular Heterogeneity ◽  
Cell Type ◽  
Crop Species ◽  
Cell Functions ◽  
Cell Type Specific ◽  
Type Specification ◽  
Accessible Chromatin

ABSTRACTCis-regulatory elements (CREs) encode the genomic blueprints for coordinating spatiotemporal gene expression programs underlying highly specialized cell functions. To identify CREs underlying cell-type specification and developmental transitions, we implemented single-cell sequencing of Assay for Transposase Accessible Chromatin in an atlas of Zea mays organs. We describe 92 distinct states of chromatin accessibility across more than 165,913 putative CREs, 56,575 cells, and 52 known cell-types in maize using a novel implementation of regularized quasibinomial logistic regression. Cell states were largely determined by combinatorial accessibility of transcription factors (TFs) and their binding sites. A neural network revealed that cell identity could be accurately predicted (>0.94) solely based on TF binding site accessibility. Co-accessible chromatin recapitulated higher-order chromatin interactions, with distinct sets of TFs coordinating cell type-specific regulatory dynamics. Pseudotime reconstruction and alignment with Arabidopsis thaliana trajectories identified conserved TFs, associated motifs, and cis-regulatory regions specifying sequential developmental progressions. Cell-type specific accessible chromatin regions were enriched with phenotype-associated genetic variants and signatures of selection, revealing the major cell-types and putative CREs targeted by modern maize breeding. Collectively, our analysis affords a comprehensive framework for understanding cellular heterogeneity, evolution, and cis-regulatory grammar of cell-type specification in a major crop species.

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