Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “single cell analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed2005

Pathogenesis of Hodgkin's lymphoma.

In Hodgkin's lymphoma (HL), the B cell origin of the tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, has been disclosed by molecular single cell analysis about 10 yr ago. This finding formed the basis for various studies aimed to better understand the pathogenesis of this peculiar malignancy and the pathophysiology of the HRS cells. Work of our groups in this regard was focussed recently on two main topics, namely the study of differential gene expression in HRS cells and the pathogenesis of composite lymphomas. Composite lymphomas are combinations of HL and B cell non-Hodgkin lymphomas, that turned out to be often clonally related. By molecular analysis of several composite lymphomas for potential transforming events, we identified examples of both shared as well as distinct transforming events. Comparing gene expression profiles of HL-derived cell lines with the corresponding profiles from other B cell lymphomas and normal B cell subsets revealed a global down-regulation of the B cell-specific gene expression signature in HRS cells. Moreover, we identifed aberrant expression and activity of multiple receptor tyrosine kinases in HRS cells of classical and to a lesser extend lymphocyte predominant HL, which appears to be a unique feature of HL, and may offer novel strategies for treatment.

B-Lymphocytes↗
PubMed1992

Large-cell "mixed-phenotype" lymphoma in AIDS. Identification of a CD5-expressing subset of B-cell non-Hodgkin's lymphoma.

We have characterized cells from an AIDS-associated non-Hodgkin's lymphoma (NHL). We found a malignant CD5+ B cell (approximately three-fourths of cells), with the balance of cells comprised of T cells having an activated phenotype. The lymphoma was unusual, in that all cells bear "T-lineage" markers, CD3 and CD5, and "B-lineage" markers, CD19 and CD20. Thus, conventional immunohistologic techniques were insufficient to type this mixture of cells; single-cell analysis was required. These "mixed-phenotype" lymphomas may occur frequently in AIDS-associated NHL. Our results show striking similarity to those obtained in the analysis of certain murine CD5+ B-cell lymphomas, suggesting that the study of lymphomagenesis in the mouse may aid in the understanding of AIDS-associated NHL.

Antigens, CD↗
PubMed2002

The molecular architecture of calcium microdomains in rat cardiomyocytes.

We have used standard indirect immunofluorescence techniques in combination with wide-field microscopy and image deconvolution to assess the distribution of proteins implicated in excitation-contraction coupling and Ca(2+) homeostasis in adult rat cardiomyocytes. We begin by discussing our earlier results and summarizing what is known about the molecular architecture of this species to provide a rationale for the work presented here. The previous results showed that the dyads contain Ca(2+) channels and ryanodine receptors, but few Na(+) channels or Na(+)/Ca(2+) exchangers. The latter proteins were not colocalized elsewhere on the membrane, and we have now found that they appear to be minimally associated with caveolin-3. None of the molecules examined are distributed uniformly in the membranes in which they are located but are organized into discrete clusters attached to the underlying cytoskeleton, an arrangement that, at the level of light microscopy, does not appear to be affected by the enzymatic dissociation used to study single cells. Analysis of how the clusters are organized and distributed throughout the volume of the cell suggests that there may be differences in excitation-contraction coupling between the cell surface and the interior.

Animals↗
PubMed1996

Cytochemical colocalization and quantitation of phenotypic and genotypic characteristics in individual bacterial cells.

The widely accepted view that most bacterial species have yet to be cultivated in vitro has gained support from recent ribosomal DNA-based environmental studies. To enable elucidation of the phenotypes of organisms recognized solely by molecular genetic techniques, we developed and evaluated cytochemical methods which colocalize phenotypic properties with in situ rRNA probe hybridization signals. Application of these methods to artificial mixtures of Pseudomonas putida and Escherichia coli or Vibrio vulnificus showed that biochemical properties, such as the cytochrome oxidase reaction and specific substrate-enhanced tetrazolium salt reduction, can be assigned to cells identified by signals from determinative fluorescent rRNA probe binding. By doing the reactions directly on the stage of an inverted microscope and monitoring reaction product formation with a charge-coupled device video camera, it was possible to determine the kinetics of oxidizable substrate utilization in single cells. Analysis of digitized images permitted quantitative study of the relationship between rRNA signal strength and the rate of tetrazolium salt reduction. The approach used in this study opens up new opportunities to investigate the biochemistry, physiology, and behavior of both culturable and nonculturable bacteria in their natural environments.

Bacteria↗
PubMed2001

Membrane permeabilization in relation to inactivation kinetics of Lactobacillus species due to pulsed electric fields.

Membrane permeabilization due to pulsed electric field (PEF) treatment of gram-positive Lactobacillus cells was investigated by using propidium iodide uptake and single-cell analysis with flow cytometry. Electric field strength, energy input, treatment time, and growth phase affected membrane permeabilization of Lactobacillus plantarum during PEF treatment. A correlation between PEF inactivation and membrane permeabilization of L. plantarum cells was demonstrated, whereas no relationship was observed between membrane permeabilization and heat inactivation. The same results were obtained with a Lactobacillus fermentum strain, but the latter organism was more PEF resistant and exhibited less membrane permeabilization, indicating that various bacteria have different responses to PEF treatment. While membrane permeabilization was the main factor involved in the mechanism of inactivation, the growth phase and the acidity of the environment also influenced inactivation. By using flow cytometry it was possible to sort cells in the L. plantarum population based on different cell sizes and shapes, and the results were confirmed by image analysis. An apparent effect of morphology on membrane permeabilization was observed, and larger cells were more easily permeabilized than smaller cells. In conclusion, our results indicate that the ability of PEF treatment to cause membrane permeabilization is an important factor in determining inactivation. This finding should have an effect on the final choice of the processing parameters used so that all microorganisms can be inactivated and, consequently, on the use of PEF treatment as an alternative method for preserving food products.

Cell Membrane Permeability↗
PubMed2001

Carbon limitation induces sigma(S)-dependent gene expression in Pseudomonas fluorescens in soil.

Recent studies employing reporter gene technology indicate that the availabilities of the major nutrients nitrogen, phosphate, and iron to Pseudomonas are not severely limited in bulk soil. Indirect evidence has pointed to carbon limitation as a severe nutritional stress in this environment. We show that a plasmid (pGM115)-borne transcriptional fusion between the sigma(S)-dependent Escherichia coli promoter P(fic) and lacZ functions as a reliable reporter for carbon availability in Pseudomonas fluorescens. When P. fluorescens strain DF57(pGM115) was introduced into bulk soil, carbon-limiting conditions were indicated by citrate-repressible induction of beta-galactosidase activity. To address carbon availability at the single-cell level, we developed an immunofluorescence double-staining procedure for individual DF57 cells expressing beta-galactosidase from P(fic). Changes in cell size and expression of beta-galactosidase were analyzed by flow cytometry. Cells extracted from soil microcosms reduced their size less than carbon-starved cells in pure culture and showed an increased tendency to aggregate. The single-cell analysis revealed that for cells residing in soil, the expression of beta-galactosidase became heterogeneous and only a DF57 subpopulation appeared to be carbon limited. In soil amended with barley straw, limited nitrogen availability has been determined by use of the bioluminescent reporter strain P. fluorescens DF57-N3. We used strain DF57-N3(pGM115) as a double reporter for carbon and nitrogen limitation that allowed us to study the dynamics of carbon and nitrogen availabilities in more detail. In straw-amended soil beta-galactosidase activity remained low, while nitrogen limitation-dependent bioluminescence appeared after a few days. Hence, nitrogen became limited under conditions where carbon resources were not completely exhausted.

Bacterial Proteins↗
PubMed2005

Incomplete activation of macrophage apoptosis during intracellular replication of Legionella pneumophila.

The ability of the intracellular bacterium Legionella pneumophila to cause disease is totally dependent on its ability to modulate the biogenesis of its phagosome and to replicate within alveolar cells. Upon invasion, L. pneumophila activates caspase-3 in macrophages, monocytes, and alveolar epithelial cells in a Dot/Icm-dependent manner that is independent of the extrinsic or intrinsic pathway of apoptosis, suggesting a novel mechanism of caspase-3 activation by this intracellular pathogen. We have shown that the inhibition of caspase-3 prior to infection results in altered biogenesis of the L. pneumophila-containing phagosome and in an inhibition of intracellular replication. In this report, we show that the preactivation of caspase-3 prior to infection does not rescue the intracellular replication of L. pneumophila icmS, icmR, and icmQ mutant strains. Interestingly, preactivation of caspase-3 through the intrinsic and extrinsic pathways of apoptosis in both human and mouse macrophages inhibits intracellular replication of the parental stain of L. pneumophila. Using single-cell analysis, we show that intracellular L. pneumophila induces a robust activation of caspase-3 during exponential replication. Surprisingly, despite this robust activation of caspase-3 in the infected cell, the host cell does not undergo apoptosis until late stages of infection. In sharp contrast, the activation of caspase-3 by apoptosis-inducing agents occurs concomitantly with the apoptotic death of all cells that exhibit caspase-3 activation. It is only at a later stage of infection, and concomitant with the termination of intracellular replication, that the L. pneumophila-infected cells undergo apoptotic death. We conclude that although a robust activation of caspase-3 is exhibited throughout the exponential intracellular replication of L. pneumophila, apoptotic cell death is not executed until late stages of the infection, concomitant with the termination of intracellular replication.

Animals↗
PubMed1999

Intrinsic human immunodeficiency virus type 1 resistance of hematopoietic stem cells despite coreceptor expression.

Interactions of human immunodeficiency virus type 1 (HIV-1) with hematopoietic stem cells may define restrictions on immune reconstitution following effective antiretroviral therapy and affect stem cell gene therapy strategies for AIDS. In the present study, we demonstrated mRNA and cell surface expression of HIV-1 receptors CD4 and the chemokine receptors CCR-5 and CXCR-4 in fractionated cells representing multiple stages of hematopoietic development. Chemokine receptor function was documented in subsets of cells by calcium flux in response to a cognate ligand. Productive infection by HIV-1 via these receptors was observed with the notable exception of stem cells, in which case the presence of CD4, CXCR-4, and CCR-5, as documented by single-cell analysis for expression and function, was insufficient for infection. Neither productive infection, transgene expression, nor virus entry was detectable following exposure of stem cells to either wild-type HIV-1 or lentivirus constructs pseudotyped in HIV-1 envelopes of macrophage-tropic, T-cell-tropic, or dualtropic specificity. Successful entry into stem cells of a vesicular stomatitis virus G protein-pseudotyped HIV-1 construct demonstrated that the resistance to HIV-1 was mediated at the level of virus-cell membrane fusion and entry. These data define the hematopoietic stem cell as a sanctuary cell which is resistant to HIV-1 infection by a mechanism independent of receptor and coreceptor expression that suggests a novel means of cellular protection from HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed2026

Integrative multi-omics profiling of insomnia-related molecular features reveals microbiome, immune, and therapy-relevant heterogeneity in colorectal cancer.

Emerging evidence implicates insomnia as a potential risk factor in carcinogenesis, potentially involving systemic inflammation, circadian disruption, and microbiome alterations. However, the molecular associations linking insomnia-related features to colorectal cancer (CRC), particularly with respect to tumor biology, immune microenvironmental states, and therapy-relevant phenotypes, remain largely unexplored. Multi-omics integration of genomic, transcriptomic, and microbiome data from 3,026 CRC patients across seven independent cohorts, including a large, well-annotated Clinical Omics study of Colorectal Cancer in China (COCC) cohort, enabled insomnia-based molecular classification through unsupervised non-negative matrix factorization (NMF) clustering. The insomnia subtype (IS) was biologically characterized via pathway enrichment, immune deconvolution, microbial profiling, and single-cell transcriptomics. Furthermore, an insomnia score (ISscore) was developed and validated in multiple cohorts for risk stratification and assessment of treatment-response-related indicators in CRC. Unsupervised clustering revealed two distinct molecular subtypes (IS1/IS2), with IS2 demonstrating significantly poorer survival. IS2 exhibited marked activation of EMT/angiogenesis pathways versus cell cycle activation in IS1. The IS2 microenvironment showed increased immunosuppression-related infiltration and exhausted T cell signatures, together with intratumoral microbiome variation characterized by depletion of Ruminococcaceae UCG-002 and enrichment of Hungatella/Selenomonas. The ISscore system stratified survival risk and was associated with computational indicators of immunotherapy response. Single-cell analysis nominated PPIA-BSG as a potential cell-cell communication signal involving high-ISscore tumor cells, CXCL12+ endothelial cells, and CLEC9A+ dendritic cell subsets. This multi-omics characterization of insomnia-CRC interplay suggests that insomnia-related molecular features are associated with an immunologically distinct and microbiome-altered tumor ecosystem. The ISscore provides a reproducible framework for capturing insomnia-related molecular heterogeneity, supporting risk stratification and future evaluation of therapy-relevant phenotypes.IMPORTANCEChronic insomnia affects millions, but it is not typically considered a cancer risk factor. Our study, analyzing vast biological data from over 3,000 colorectal cancer patients, uncovers a potential link between a person's predisposition to insomnia and their risk of developing this disease. This suggests that the biological pathways related to sleep may play a role in cancer development. Understanding this connection opens up new avenues for identifying individuals at higher risk and developing novel prevention strategies for colorectal cancer.

colorectal cancer↗
PubMed2026

Ascites reprograms innate lymphoid immune cells in ovarian cancer by promoting ILC2 enrichment and dysfunctional NK-cell states.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is commonly accompanied by malignant ascites, a clinically relevant tumor niche that promotes immune evasion, metastasis, and treatment resistance. Although natural killer (NK)-cell dysfunction has been described in ovarian cancer, the broader innate lymphoid landscape of ascites and the mechanisms linking ascites-derived signals to innate immune suppression remain insufficiently resolved. METHODS: We performed single-cell RNA sequencing of NK/innate lymphoid cells from ovarian cancer ascites to define cellular heterogeneity and differentiation states. Functional assays assessed NK-cell cytotoxicity, degranulation, and receptor expression following exposure to patient-derived ascites, with or without transforming growth factor-β (TGF-β) receptor inhibition. Proteomic profiling was used to characterize the soluble ascites milieu, and clinical associations were examined for innate lymphoid subsets. RESULTS: Single-cell analysis identified eight transcriptionally distinct NK/innate lymphoid states, including cytotoxic, precursor, early-like, tolerant/immunoregulatory, regulatory, proinflammatory, and innate lymphoid populations. Ovarian cancer ascites was characterized by depletion of cytotoxic and precursor NK-cell states together with enrichment of early-like, tolerant, regulatory, pro-inflammatory, and innate lymphoid cell (ILC) populations. Trajectory analysis indicated impaired maturation toward terminally differentiated cytotoxic NK cells. Notably, ascites contained an expanded population of programmed cell death protein 1 (PD-1)+ ILC2s, which were more abundant in patients with shorter progression-free survival. In functional assays, short-term exposure of healthy donor NK cells to ascites suppressed degranulation and tumor-cell killing, reduced expression of activating receptors including NKp30 and DNAM-1, increased inhibitory receptor expression, and shifted NK cells toward a CD56highCD16low phenotype. Proteomic profiling supported a soluble milieu consistent with type 2 immune skewing and NK-cell suppression. Importantly, TGF-β receptor inhibition partially restored NK-cell activation and function in the presence of ascites. CONCLUSIONS: HGSOC ascites establishes a type 2-skewed immunoregulatory niche that coordinately drives NK cell dysfunction and PD-1+ ILC2 accumulation. The findings identify TGF-β-linked suppression and ascites-associated immune regulators as candidate immunotherapeutic vulnerabilities for restoring antitumor immunity in ovarian cancer.

Humans↗
PubMed2004

Transgenic upregulation of IK1 in the mouse heart leads to multiple abnormalities of cardiac excitability.

To assess the functional significance of upregulation of the cardiac current (IK1), we have produced and characterized the first transgenic (TG) mouse model of IK1 upregulation. To increase IK1 density, a pore-forming subunit of the Kir2.1 (green fluorescent protein-tagged) channel was expressed in the heart under control of the alpha-myosin heavy chain promoter. Two lines of TG animals were established with a high level of TG expression in all major parts of the heart: line 1 mice were characterized by 14% heart hypertrophy and a normal life span; line 2 mice displayed an increased mortality rate, and in mice < or =1 mo old, heart weight-to-body weight ratio was increased by >100%. In adult ventricular myocytes expressing the Kir2.1-GFP subunit, IK1 conductance at the reversal potential was increased approximately 9- and approximately 10-fold in lines 1 and 2, respectively. Expression of the Kir2.1 transgene in line 2 ventricular myocytes was heterogeneous when assayed by single-cell analysis of GFP fluorescence. Surface ECG recordings in line 2 mice revealed numerous abnormalities of excitability, including slowed heart rate, premature ventricular contractions, atrioventricular block, and atrial fibrillation. Line 1 mice displayed a less severe phenotype. In both TG lines, action potential duration at 90% repolarization and monophasic action potential at 75-90% repolarization were significantly reduced, leading to neuronlike action potentials, and the slow phase of the T wave was abolished, leading to a short Q-T interval. This study provides a new TG model of IK1 upregulation, confirms the significant role of IK1 in cardiac excitability, and is consistent with adverse effects of IK1 upregulation on cardiac electrical activity.

Action Potentials↗
PubMed2003

Expansion and proliferation of skin-homing T cells in atopic dermatitis as assessed at the single cell level.

BACKGROUND: Sensitization to aeroallergens is a frequent event in patients with atopic dermatitis (AD). The role of allergen-specific T cells in the pathogenesis of AD is, however, not fully clear. A detailed immunological characterization of allergen-specific T cells able to migrate to inflamed skin might therefore be helpful in determining the relevance of allergen-specific T cells to clinical symptoms. OBJECTIVE: To establish a simple assay to simultaneously monitor the expression of skin-related homing molecules and their proliferative response to an allergen on peripheral T cells. To evaluate whether this assay is able to identify AD patients in whom exposure to an allergen induces dermatitis. METHODS: The expression of CLA, CD7 and CD4 was simultaneously measured by flow cytometry with the DNA content as a parameter of proliferation at the single cell level. House dust mite antigen (DerP) and tetanus toxoid (TT) were used as antigens. RESULTS: CD4+ CLA+ CD7-, but not CLA- T cells from patients with AD proliferated and expanded following DerP stimulation. In contrast, TT stimulation resulted in proliferation of both, CLA+ and CLA- T cells from both, atopic and healthy donors. CONCLUSIONS: Single cell analysis revealed a predominant localization of allergen-reactive T cells within the CD7- CLA+ CD4+ T cell subset in AD. Thus, this simple assay not only confirms previously published results, but also extends our knowledge on the biology of CLA and CD7 cells in AD. Ultimately, this will be helpful in classifying those patients who might benefit from allergen avoidance therapies.

Adult↗
PubMed1992

An increased ability to generate hydrogen peroxide in certain polymorphonuclear leukocytes in neonates.

We performed a quantitative assay of the hydrogen peroxide generation in polymorphonuclear leukocytes using single cell analysis by flow cytometry. The study population included premature neonates (n = 10), term neonates (n = 28) and healthy adults (n = 29). The ability to generate hydrogen peroxide in neonatal polymorphonuclear leukocytes was totally reduced compared with adults, however, some polymorphonuclear leukocytes in neonates demonstrated highly accentuated hydrogen peroxide generation.

Adult↗
PubMed1982

Monoclonal antimacrophage antibodies: human pulmonary macrophages express HLA-DR (Ia-like) antigens in culture.

Study of human macrophages and their role in disease has been hampered by lack of well-characterized tissue macrophages. We describe a simple procedure to obtain viable adherent cells in good yield from resected lung, characterize the cells as greater than 95% macrophage by standard criteria, and document expression of marker properties previously described in rodent macrophages. Human pulmonary macrophages were used to produce monoclonal antibodies and to study expression of HLA-A,B,C, HLA-DR, and related antigens. A new monoclonal mouse antibody, 18, showed restricted binding to macrophages from human lung or blood and to B lymphoid cells, but did not bind to closely related cells. With antibody 18 and other monoclonal antibodies of known specificity, DA2 and Genox 3.53, we showed that a remarkably high proportion of human pulmonary macrophages express HLA-DR framework and DC1 polymorphic determinants in culture. Although the macrophages differed in source and in their state of activation, single cell analysis revealed no heterogeneity in antigen expression.

Antibodies, Monoclonal↗
PubMed2026

Unveiling m7G modification patterns and causal drivers governing intracranial aneurysm rupture risk through multi-omics validation and m7G-MeRIP-seq profiling.

Intracranial aneurysm (IA) rupture causes severe brain hemorrhage with high mortality, yet its molecular drivers remain unclear and better risk prediction is urgently needed. Using transcriptomics, single-cell analysis, and genetic data, we investigated the role of N7-methylguanosine (m7G) RNA modification in IA. We identified distinct m7G modification patterns, validated their methylation features in patient samples, and incorporated these patterns into a machine learning-based rupture prediction model. The presence and characteristics of m7G patterns significantly improved model performance, achieving high predictive accuracy across three independent cohorts (AUC 0.91-0.95). Genetic analyses further identified three causal m7G-related genes (NSUN2, IFIT5, SNUPN), and laboratory experiments confirmed their altered expression and methylation in ruptured aneurysms. Overall, our findings demonstrate that m7G modifications play a key role in IA rupture. The validated prediction model offers strong clinical potential for rupture risk assessment, and the identified genes represent promising therapeutic targets.

Humans↗
PubMed2026

Integrative genetic and transcriptomic analyses prioritize CDC16 as a candidate marker for gastric cancer.

BackgroundGastric cancer (GC) remains a major cause of cancer-related mortality, and biomarkers for early detection are needed.MethodsStomach and blood expression quantitative trait loci were integrated with two GC genome-wide association studies using Mendelian randomization (MR), Bayesian colocalization, and summary-data-based MR/heterogeneity in dependent instruments (SMR/HEIDI) testing. Bulk and single-cell transcriptomic analyses characterized candidate expression and lesion-associated patterns. CDC16 protein expression was evaluated by immunohistochemistry in 53 paired GC and non-neoplastic tissues, followed by paired and exploratory receiver operating characteristic analyses.ResultsMR prioritized PILRB, CDC16, and GABPB1-AS1; SMR/HEIDI provided complementary support, while colocalization for CDC16 and GABPB1-AS1 was suggestive and model-dependent. Bulk-tissue CDC16 abundance was higher in GC, but the modest TCGA-STAD tumor-normal difference (log2FC = 0.210, FDR = 0.019) was attenuated after proliferation adjustment (log2FC = -0.002, FDR = 0.987), indicating close coupling with proliferative activity. Single-cell analysis localized CDC16 predominantly to epithelial populations, and the proportion of CDC16-detectable epithelial cells increased across lesion categories (&#x3c1; = 0.735; permutation P = 0.031). CDC16 H-scores were higher in GC than in paired non-neoplastic tissues (161.15 &#xb1; 45.11 vs 102.15 &#xb1; 54.50; P < 0.001), with higher cancer-tissue scores in 41 of 53 cases. Exploratory AUC was 0.794 (95% CI, 0.704-0.874; sensitivity, 66.0%; specificity, 79.2%).ConclusionsConvergent genetic, transcriptomic, and protein-level evidence prioritizes CDC16 as a GC-associated candidate tissue marker whose expression is closely linked to proliferative activity. Prospective validation in independent cohorts, including appropriate disease controls and blood-based evaluation, is warranted.

Stomach Neoplasms↗
PubMed2002

Cortical dysgenesis and epilepsy.

Cortical dysgenesis (CD) describes a wide spectrum of brain anomalies that involve abnormal development of the cerebral cortex. There is a strong association between CD and epilepsy, and it comprises a significant proportion of children and adults whose epilepsy cannot be controlled with medications. There has been intense effort to define the relationship between CD and epilepsy so that more effective therapies can be devised. These efforts have ranged from detailed study of people with CD and epilepsy from a clinical standpoint to single-cell analysis of mRNA expression and postsynaptic receptor function. Animal models have also been developed to mimic certain aspects of CD in a situation when quantitative, controlled, and interventional experiments can be performed that would not be possible in a clinical setting. This review will give an overview of human CD syndromes and their causes, when possible, and describe some specific abnormalities in dysplastic cortex that may underlie its epileptogenic potential. It will also review several animal models of CD that have been studied mechanistically from the standpoint of epileptogenesis. In conclusion, some general trends will be proposed based on human and animal studies to encapsulate our current understanding of CD and how it causes epilepsy.

Animals↗
PubMed2006

Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells.

Despite the importance of thymic stromal cells to T-cell development, relatively little is known about their biology. Here, we use single-cell analysis of stromal cells to analyze extensive changes in the number and composition of thymic stroma throughout life, revealing a surprisingly dynamic population. Phenotypic progression of thymic epithelial subsets was assessed at high resolution in young mice to provide a developmental framework. The cellular and molecular requirements of adult epithelium were studied, using various mutant mice to demonstrate new cross talk checkpoints dependent on RelB in the cortex and CD40 in the medulla. With the use of Ki67 and BrdU labeling, the turnover of thymic epithelium was found to be rapid, but then diminished on thymic involution. The various defects in stromal turnover and composition that accompanied involution were rapidly reversed following sex steroid ablation. Unexpectedly, mature cortical and medullary epithelium showed a potent capacity to stimulate naive T cells, comparable to that of thymic dendritic cells. Overall, these studies show that the thymic stroma is a surprisingly dynamic population and may have a more direct role in negative selection than previously thought.

Aging↗