scholarly journals Derivation of marker gene signatures from human skin and their use in the interpretation of the transcriptional changes associated with dermatological disorders

2017 ◽  
Vol 241 (5) ◽  
pp. 600-613 ◽  
Author(s):  
Barbara B Shih ◽  
Ajit J Nirmal ◽  
Denis J Headon ◽  
Arne N Akbar ◽  
Neil A Mabbott ◽  
...  
Keyword(s):  
Human Skin ◽  
Marker Gene ◽  
Gene Signatures ◽  
Transcriptional Changes ◽  
Dermatological Disorders

The histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development

2021 ◽  
Vol 218 (12) ◽  
Author(s):  
Daniel B. Stamos ◽  
Lauren M. Clubb ◽  
Apratim Mitra ◽  
Laura B. Chopp ◽  
Jia Nie ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Histone Demethylase ◽  
Interferon Response ◽  
Gene Promoters ◽  
Critical Function ◽  
Gene Signatures ◽  
Transcriptional Changes ◽  
Cell Gene

Analysis of the transcriptional profiles of developing thymocytes has shown that T lineage commitment is associated with loss of stem cell and early progenitor gene signatures and the acquisition of T cell gene signatures. Less well understood are the epigenetic alterations that accompany or enable these transcriptional changes. Here, we show that the histone demethylase Lsd1 (Kdm1a) performs a key role in extinguishing stem/progenitor transcriptional programs in addition to key repressive gene programs during thymocyte maturation. Deletion of Lsd1 caused a block in late T cell development and resulted in overexpression of interferon response genes as well as genes regulated by the Gfi1, Bcl6, and, most prominently, Bcl11b transcriptional repressors in CD4+CD8+ thymocytes. Transcriptional overexpression in Lsd1-deficient thymocytes was not always associated with increased H3K4 trimethylation at gene promoters, indicating that Lsd1 indirectly affects the expression of many genes. Together, these results identify a critical function for Lsd1 in the epigenetic regulation of multiple repressive gene signatures during T cell development.

scholarly journals An NMRA-Like Protein Regulates Gene Expression in Phytophthora capsici to Drive the Infection Cycle on Tomato

2018 ◽  
Vol 31 (6) ◽  
pp. 665-677 ◽  
Author(s):  
Jasmine Pham ◽  
Remco Stam ◽  
Victor Martinez Heredia ◽  
Michael Csukai ◽  
Edgar Huitema
Keyword(s):  
Gene Expression ◽  
Crop Production ◽  
Large Scale ◽  
Phytophthora Capsici ◽  
Marker Gene ◽  
Infection Cycle ◽  
Distinct Evolutionary Lineage ◽  
Phytophthora Spp ◽  
Transcriptional Changes

Phytophthora spp. cause devastating disease epidemics on important crop plants and pose a grave threat to global crop production. Critically, Phytophthora pathogens represent a distinct evolutionary lineage in which pathogenicity has been acquired independently. Therefore, there is an urgent need to understand and disrupt the processes that drive infection if we aspire to defeat oomycete pathogens in the field. One area that has received little attention thus far in this respect is the regulation of Phytophthora gene expression during infection. Here, we characterize PcNMRAL1 (Phyca11_505845), a homolog of the Aspergillus nidulans nitrogen metabolite repression regulator NMRA and demonstrate a role for this protein in progression of the Phytophthora capsici infection cycle. PcNmrAL1 is coexpressed with the biotrophic marker gene PcHmp1 (haustorial membrane protein 1) and, when overexpressed, extends the biotrophic infection stage. Microarray analyses revealed that PcNmrAL1 overexpression in P. capsici leads to large-scale transcriptional changes during infection and in vitro. Importantly, detailed analysis reveals that PcNmrAL1 overexpression induces biotrophy-associated genes while repressing those associated with necrotrophy. In addition to factors controlling transcription, translation, and nitrogen metabolism, PcNMRAL1 helps regulate the expression of a considerable effector repertoire in P. capsici. Our data suggests that PcNMRAL1 is a transcriptional regulator that mediates the biotrophy to necrotrophy transition. PcNMRAL1 represents a novel factor that may drive the Phytophthora disease cycle on crops. This study provides the first insight into mechanisms that regulate infection-related processes in Phytophthora spp. and provides a platform for further studies aimed at disabling pathogenesis and preventing crop losses.

A web-like network of type vi collagen in human skin is revealed by immuno-electron microscopy

1988 ◽  
Vol 46 ◽  
pp. 382-383
Author(s):  
Douglas R. Keene ◽  
Robert W. Glanville ◽  
Eva Engvall
Keyword(s):  
Electron Microscopy ◽  
Monoclonal Antibody ◽  
Human Skin ◽  
Basement Membranes ◽  
Primary Antibody ◽  
Fat Cells ◽  
Secondary Antibody ◽  
Type Vi Collagen ◽  
Dermal Matrix ◽  
Immuno Electron Microscopy

A mouse monoclonal antibody (5C6) prepared against human type VI collagen (1) has been used in this study to immunolocalize type VI collagen in human skin. The enbloc method used involves exposing whole tissue pieces to primary antibody and 5 nm gold conjugated secondary antibody before fixation, and has been described in detail elsewhere (2).Biopsies were taken from individuals ranging in age from neonate to 65 years old. By immuno-electron microscopy, type VI collagen is found to be distributed as a fine branching network closely associated with (but not attached to) banded collagen fibrils containing types I and III collagen (Fig. 1). It appears to enwrap fibers, to weave between individual fibrils within a fiber, and to span the distance separating fibers, creating a “web-like network” which entraps fibers within deep papillary and reticular dermal layers (Fig. 2). Relative to that in the dermal matrix, the concentration of type VI collagen is higher around endothelial basement membranes limiting the outer boundaries of nerves, capillaries, and fat cells (Fig. 3).

Effect of Acetone and Kerosene on Skin Ultrastructure

1972 ◽  
Vol 30 ◽  
pp. 92-93
Author(s):  
A. P. Lupulescu ◽  
H. Pinkus ◽  
D. J. Birmingham
Keyword(s):  
Electron Microscopy ◽  
Human Skin ◽  
Osmium Tetroxide ◽  
Human Epidermis ◽  
Ultrastructural Changes ◽  
Chemical Agents ◽  
Skin Ultrastructure ◽  
Volar Surface

Our laboratory is engaged in the study of the effect of different chemical agents on human skin, using electron microscopy. Previous investigations revealed that topical use of a strong alkali (NaOH 1N) or acid (HCl 1N), induces ultrastructural changes in the upper layers of human epidermis. In the current experiments, acetone and kerosene, which are primarily lipid solvents, were topically used on the volar surface of the forearm of Caucasian and Negro volunteers. Skin specimens were bioptically removed after 90 min. exposure and 72. hours later, fixed in 3% buffered glutaraldehyde, postfixed in 1% phosphate osmium tetroxide, then flat embedded in Epon.

Changes in corneocyte element concentrations occur in skin inner stratum corneum

1990 ◽  
Vol 48 (2) ◽  
pp. 146-147
Author(s):  
R. R. Warner
Keyword(s):  
Stratum Corneum ◽  
Human Skin ◽  
Element Concentration ◽  
Skin Barrier ◽  
Barrier Properties ◽  
Brick Wall ◽  
Inorganic Elements ◽  
Dry Skin ◽  
Skin Biopsies ◽  
Intercellular Lipid

Keratinocytes undergo maturation during their transit through the viable layers of skin, and then abruptly transform into flattened, anuclear corneocytes that constitute the cellular component of the skin barrier, the stratum corneum (SC). The SC is generally considered to be homogeneous in its structure and barrier properties, and is often shown schematically as a featureless brick wall, the “bricks” being the corneocytes, the “mortar” being intercellular lipid. Previously we showed the outer SC was not homogeneous in its composition, but contained steep gradients of the physiological inorganic elements Na, K and Cl, likely originating from sweat salts. Here we show the innermost corneocytes in human skin are also heterogeneous in composition, undergoing systematic changes in intracellular element concentration during transit into the interior of the SC.Human skin biopsies were taken from the lower leg of individuals with both “good” and “dry” skin and plunge-frozen in a stirred, cooled isopentane/propane mixture.

Desmosomal distribution in the epidermis of a non-contracting human skin equivalent

1992 ◽  
Vol 50 (1) ◽  
pp. 896-897
Author(s):  
L.X. Oakford ◽  
S.D. Dimitrijevich ◽  
R. Gracy
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Skin Equivalent ◽  
Tissue Component ◽  
Intact Skin ◽  
Similar Sequence ◽  
Sequence Of Events ◽  
Suprabasal Keratinocytes ◽  
Human Skin Equivalent

In intact skin the epidermal layer is a dynamic tissue component which is maintained by a basal layer of mitotically active cells. The protective upper epidermis, the stratum corneum, is generated by differentiation of the suprabasal keratinocytes which eventually desquamate as anuclear comeocytes. A similar sequence of events is observed in vitro in the non-contracting human skin equivalent (HSE) which was developed in this lab (1). As a part of the definition process for this model of living skin we are examining its ultrastructural features. Since desmosomes are important in maintaining cell-cell interactions in stratified epithelia their distribution in HSE was examined.

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