Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters










Database
Language
Publication year range
1.
J Dent Res ; 102(5): 525-535, 2023 05.
Article in English | MEDLINE | ID: mdl-36726292

ABSTRACT

Saliva-secreting and transporting cells are part of the complex cellular milieu of the human salivary gland, where they play important roles in normal glandular physiology and diseased states. However, comprehensive molecular characterization, particularly at single-cell resolution, is still incomplete, in part due to difficulty in procuring normal human tissues. Here, we perform an in-depth analysis of male and female adult human submandibular gland (SMG) samples by bulk RNA sequencing (RNA-seq) and examine the molecular underpinnings of the heterogeneous cell populations by single-cell (sc) RNA-seq. Our results from scRNA-seq highlight the remarkable diversity of clusters of epithelial and nonepithelial cells that reside in the SMG that is also faithfully recapitulated by deconvolution of the bulk-RNA data sets. Our analyses reveal complex transcriptomic heterogeneity within both the ductal and acinar subpopulations and identify atypical SMG cell types, such as mucoacinar cells that are unique to humans and ionocytes that have been recently described in the mouse. We use CellChat to explore ligand-receptor interactome predictions that likely mediate crucial cell-cell communications between the various cell clusters. Finally, we apply a trajectory inference method to investigate specific cellular branching points and topology that offers insights into the dynamic and complex differentiation process of the adult SMG. The data sets and the analyses herein comprise an extensive wealth of high-resolution information and a valuable resource for a deeper mechanistic understanding of human SMG biology and pathophysiology.


Subject(s)
Submandibular Gland , Transcriptome , Humans , Male , Mice , Female , Animals , Salivary Glands , Gene Expression Profiling , Cell Differentiation
2.
J Dent Res ; 102(3): 340-348, 2023 03.
Article in English | MEDLINE | ID: mdl-36348499

ABSTRACT

Salivary gland (SG) development, maturation, and homeostasis require coordinated roles of transcription factors (TFs) that dictate specific cell identities and fate. The ETS family of proteins are important transcriptional drivers of diverse cell lineages, tissue development, and differentiation programs and hence are also likely to play an important role in the SG. Here we have leveraged genomic and epigenomic data of the SG to examine the expression profile of ETS genes and identified 2 closely related paralogs, Elf5 and Ehf, that are highly expressed in distinct epithelial subpopulations. By using a well-defined mouse knockout model of Elf5, we show that Elf5, despite its enriched expression in the acinar cells, is functionally dispensable for maintaining the homeostatic state of the adult SG epithelium. The lack of a discernible phenotype of the Elf5-null SG might be due to possible functional redundancy with Ehf or other ETS factors. To probe this possibility and to examine the specific consequences of Ehf loss in the SG, we used CRISPR-Cas9 to generate mice in which the DNA-binding ETS domain of Ehf is disrupted due to an insertion mutation. We demonstrate that the Ehf mutant (EhfMut) mice exhibit a distinct cellular phenotype with decreased granular convoluted tubules that are accompanied by an increased accumulation of the intercalated Sox9-positive ductal cell population. Interestingly, the ductal phenotype of the EhfMut animals is highly pronounced in males, reaffirming the established sexual dimorphism of the SG that exists in rodents. Our results show that unlike Elf5, Ehf plays a nonredundant role in directing ductal cell differentiation of the SG and highlights the phenotypic subtlety in mutant mice of closely related TFs and the importance of careful consideration of cell type-specific studies.


Subject(s)
DNA-Binding Proteins , Transcription Factors , Male , Mice , Animals , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Transcription Factors/metabolism , Salivary Glands/metabolism
3.
J Dent Res ; 100(13): 1492-1500, 2021 12.
Article in English | MEDLINE | ID: mdl-33978512

ABSTRACT

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.


Subject(s)
Epigenomics , Submandibular Gland , Animals , Mice , Parotid Gland , Salivary Glands , Sublingual Gland
4.
J Dent Res ; 98(13): 1539-1547, 2019 12.
Article in English | MEDLINE | ID: mdl-31623513

ABSTRACT

The salivary complex of mammals consists of 3 major pairs of glands: the parotid, submandibular, and sublingual glands. While the 3 glands share similar functional properties, such as saliva secretion, their differences are largely based on the types of secretions they produce. While recent studies have begun to shed light on the underlying molecular differences among the glands, few have examined the global transcriptional repertoire over various stages of gland maturation. To better elucidate the molecular nature of the parotid gland, we have performed RNA sequencing to generate comprehensive and global gene expression profiles of this gland at different stages of maturation. Our transcriptomic characterization and hierarchical clustering analysis with adult organ RNA sequencing data sets has identified a number of molecular players and pathways that are relevant for parotid gland biology. Moreover, our detailed analysis has revealed a unique parotid gland-specific gene signature that may represent important players that could impart parotid gland-specific biological properties. To complement our transcriptomic studies, we have performed single-cell RNA sequencing to map the transcriptomes of parotid epithelial cells. Interrogation of the single-cell transcriptomes revealed the degree of molecular and cellular heterogeneity of the various epithelial cell types within the parotid gland. Moreover, we uncovered a mixed-lineage population of cells that may reflect molecular priming of differentiation potentials. Overall our comprehensive studies provide a powerful tool for the discovery of novel molecular players important in parotid gland biology.


Subject(s)
Parotid Gland/cytology , Parotid Gland/metabolism , Single-Cell Analysis , Transcriptome , Animals , Mice
5.
Poult Sci ; 90(9): 1948-54, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21844259

ABSTRACT

The present study reports on layer chickens with colibacillosis in 2 commercial egg-producing farms (referred to as farm A and farm B, which were managed by the same owner and were about 1 km apart) in the middle region of the Korean peninsula. The 2 flocks were infected at the initiation of egg laying. They were characterized by no previous clinical signs but sudden mortality (2.7-4.0%), with severe lesions of septicemia and fibrinous polyserositis. Escherichia coli was isolated from the lesions of the infected birds. Serotyping tests identified isolates that belonged to somatic groups O1 (12/17), O46 (2/17), O78 (1/17), and O84 (1/17) or that were unidentified (1/17). Thirteen of 17 E. coli isolates (76.4%) obtained from 11 birds in the 2 flocks showed similar pulsed-field gel electrophoresis patterns that were arbitrarily designated as pattern A. The isolates had high frequencies of putative virulence genes including 100% [fimC (type 1 fimbriae), iucD (aerobactin synthesis), and iss (increased serum survival)], 94.1% [cva/cvi (structural genes of colicin V operon) and vat (vacuolating autotransporter toxin)], 88.2% [irp2, iron-repressible protein (yersinia bactin) synthesis, and fyuA, ferric yersinia uptake], and 82.3% [tsh (temperature-sensitive hemagglutinin)]; astA (encoding a heat-stable cytotoxin associated with enteroaggregative E. coli) was not associated with the enteric disorder. These data suggest that all chickens with colibacillosis on farms A and B were likely infected by E. coli strains that are highly pathogenic in avian species.


Subject(s)
Chickens , Escherichia coli Infections/veterinary , Escherichia coli/classification , Poultry Diseases/microbiology , Animals , Electrophoresis, Gel, Pulsed-Field/veterinary , Escherichia coli Infections/epidemiology , Escherichia coli Infections/microbiology , Female , Polymerase Chain Reaction/veterinary , Poultry Diseases/epidemiology , Republic of Korea/epidemiology , Serotyping
6.
Poult Sci ; 89(10): 2116-22, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20852102

ABSTRACT

Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) has been associated with morbidity and mortality in broiler chickens worldwide. The present study described purulent arthritis of broilers infected with Salmonella Enteritidis and investigated antibiograms and genetic characteristics of Salmonella Enteritidis isolates from epidemiologically related properties such as a hatchery and breeder farm in an attempt to elucidate the source of contamination. Clinical disease and mortality were observed in the affected broiler flock. Mortality was 5.8% until 12 d of age. The birds typically showed lameness with moderately swollen hock joints and footpads. The most prevalent lesions were severely purulent arthritis with polyserositis. Histopathology revealed moderate to severe inflammation in the synovial membrane of leg joints and visceral organs. When the antimicrobial susceptibility test was performed against 7 isolates of Salmonella Enteritidis from broilers, and relevant hatchery and breeder farms by the disk diffusion method using 18 antimicrobial agents, isolates from broiler and breeder farms had the same antibiogram characterized by multiple drug resistance to ampicillin, ceftiofur, cephalothin, gentamycin, nalidixic acid, streptomycin, sulfisoxazole, and tetracycline, whereas isolates from the hatchery were differently resistant to only nalidixic acid. Through the genetic analysis with pulsed-field gel electrophoresis using the restriction enzyme XbaI, Salmonella Enteritidis isolates from both broiler and breeder farms also showed the same PFGE pattern compared with the hatchery isolates resistant to nalidixic acid. As a result, the same PFGE profiles and antibiogram patterns among isolates from broilers and breeder farms provided direct evidence of vertical Salmonella Enteritidis transmission from the contaminated breeder farm to commercial broiler.


Subject(s)
Arthritis, Infectious/veterinary , Chickens , Poultry Diseases/microbiology , Salmonella Infections, Animal/microbiology , Salmonella enteritidis/isolation & purification , Animals , Anti-Bacterial Agents/pharmacology , Arthritis, Infectious/epidemiology , Arthritis, Infectious/microbiology , Arthritis, Infectious/transmission , Drug Resistance, Multiple, Bacterial , Infectious Disease Transmission, Vertical , Poultry Diseases/epidemiology , Poultry Diseases/transmission , Republic of Korea/epidemiology , Salmonella Infections, Animal/epidemiology , Salmonella Infections, Animal/transmission , Salmonella enteritidis/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...