How multipotent progenitors give rise to multiple cell types in defined numbers is a central question in developmental biology. Epigenetic switches, acting at single gene loci, can generate extended delays in the activation of lineage-specifying genes and impact lineage decisions and cell type output. Here, we analyzed a timed epigenetic switch controlling expression of mouse Bcl11b, a transcription factor that drives T-cell commitment, but only after a multi-day delay.
View Article and Find Full Text PDFPulmonary fibrosis, including systemic sclerosis-associated interstitial lung disease (SSc-ILD), involves myofibroblasts and SPP1 macrophages as drivers of fibrosis. Single-cell RNA sequencing has delineated fibroblast and macrophages transcriptomes, but limited insight into transcriptional control of profibrotic gene programs. To address this challenge, we analyzed multiomic snATAC/snRNA-seq on explanted SSc-ILD and donor control lungs.
View Article and Find Full Text PDFAffinity-matured plasma cells (PCs) of varying lifespans are generated through a germinal center (GC) response. The developmental dynamics and genomic programs of antigen-specific PC precursors remain to be elucidated. Here, using a model antigen in mice, we demonstrate biphasic generation of PC precursors, with those generating long-lived bone marrow PCs preferentially produced in the late phase of GC response.
View Article and Find Full Text PDFDermatomyositis is a rare auto-immune inflammatory myopathy of unknown etiology. Several environmental factors, including vaccines, have been identified as potential triggers in genetically susceptible individuals. Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the development of vaccines (mRNA and vector-based) has been the most effective tool in reducing the incidence, hospitalization rates, and mortality of COVID-19.
View Article and Find Full Text PDFAnomalies of the inferior vena cava (IVC) are an uncommon finding in the general population. A wide range of IVC anomalies has been described in the literature, the majority of which lack clinical significance. Agenesis of the IVC (AIVC) is a rare anomaly of the IVC in the general population.
View Article and Find Full Text PDFEosinophilic gastrointestinal disorders (EGIDs) refer to eosinophilic infiltration of various sections of the gastrointestinal tract in the absence of secondary causes. Diagnosis of EGID requires histological evidence of eosinophilic infiltration of the GI tract. Here, we present a case of a young male with biopsy-proven eosinophilic gastroenteritis with a concomitant established diagnosis of immune thrombocytopenic purpura (ITP).
View Article and Find Full Text PDFBoerhaave's syndrome is a rare yet serious condition associated with high mortality and morbidity. Diagnosis of this syndrome is usually done with the aid of imaging and prompt management should be initiated to improve the outcomes. Treatment for this syndrome has been mainly surgical since its discovery by Herman Boerhaave; however, multiple endoscopic approaches have been successfully used recently with the advancement of this field.
View Article and Find Full Text PDFScaffold-free 3D cell cultures (e.g. pellet cultures) are widely used in medical science, including cartilage regeneration.
View Article and Find Full Text PDFUveal melanoma (UM) is a malignant intraocular tumor that spreads to the liver in half of the cases. Since hepatic cells could play a role in the therapeutic resistance of metastatic UM, the purpose of our study was to investigate the pro-invasive role of hepatic stellate cells (HSteCs) in metastatic UM at the micro- and macro-metastatic stages. We first performed an immunostaining with the alpha-smooth muscle actin (αSMA) to localize activated HSteCs in UM liver macro-metastases from four patients.
View Article and Find Full Text PDFPurpose: The intensity of care provided to critically ill patients has been shown to be associated with mortality. In patients with traumatic brain injury (TBI), specialized neurocritical care is often required, but whether it affects clinically significant outcomes is unknown. We aimed to determine the association of the intensity of care on mortality and the incidence of withdrawal of life-sustaining therapies in critically ill patients with severe TBI.
View Article and Find Full Text PDF