A5067136011- Renal and related cancers
- Chronic Kidney Disease and Diabetes
- Cardiac Valve Diseases and Treatments
- Pluripotent Stem Cells Research
- Renal cell carcinoma treatment
- Neurogenesis and neuroplasticity mechanisms
- Single-cell and spatial transcriptomics
- Tuberous Sclerosis Complex Research
- Genetic and Kidney Cyst Diseases
- Cancer-related molecular mechanisms research
- Aortic aneurysm repair treatments
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Reproductive System and Pregnancy
- Eosinophilic Disorders and Syndromes
- MicroRNA in disease regulation
- Developmental Biology and Gene Regulation
- Aortic Disease and Treatment Approaches
- Gastrointestinal motility and disorders
- Chromatin Remodeling and Cancer
- Immune Response and Inflammation
- Cardiac and Coronary Surgery Techniques
- Congenital gastrointestinal and neural anomalies
- Mesenchymal stem cell research
- Helicobacter pylori-related gastroenterology studies
- Histiocytic Disorders and Treatments
University Hospital Cologne
2019-2025
Cincinnati Children's Hospital Medical Center
2015-2025
University of Cincinnati
2020-2024
Centrum für Integrierte Onkologie
2022
Children's Medical Center
2015-2021
TRIUMF
2015-2017
Old Dominion University
1990-1991
Single cell RNA-seq is a powerful methodology. Nevertheless there are important limitations, including the technical challenges of breaking down an organ or tissue into single suspension. Invariably this has required enzymatic incubation at 37°C, which can be expected to result in artifact changes gene expression patterns. We here describe dissociation method that uses protease with high activity cold, purified from psychrophilic microorganism. The entire procedure carried out 6°C colder,...
The respiratory system undergoes a diversity of structural, biochemical, and functional changes necessary for adaptation to air breathing at birth. To identify the heterogeneity pulmonary cell types dynamic in gene expression mediating respiration, here we perform single RNA analyses mouse lung on postnatal day 1. Using an iterative type identification strategy unbiasedly murine types. We distinct populations epithelial, endothelial, mesenchymal, immune cells, each containing subpopulations....
Significance Statement Because current management of the rapid renal-function decline in AKI is merely supportive, deeper understanding AKI-perturbed molecular pathways needed to identify targets with potential lead improved treatment. In a murine model, authors used single-cell RNA sequencing, single-molecule situ hybridization, and protein expression analyses create first comprehensive renal cell type–specific transcriptional profiles for multiple stages. Their findings revealed marked...
Adult mammalian skin wounds heal by forming fibrotic scars. We report that full-thickness injuries of reindeer antler (velvet) regenerate, whereas back forms scar. Single-cell multi-omics reveal uninjured velvet fibroblasts resemble human fetal fibroblasts, express inflammatory mediators mimicking pro-fibrotic adult and rodent fibroblasts. Consequently, injury elicits site-specific immune responses: amplify myeloid infiltration maturation during repair, adopt an immunosuppressive phenotype...
Abstract Background The evolution of antibiotic resistance in bacteria is a topic major medical importance. Evolution the result natural selection acting on variant phenotypes. Both rigid base sequence DNA and more plastic expression patterns genes present define phenotype. Results We investigated resistant E. coli when exposed to low concentrations antibiotic. show that within an isogenic population there are heritable variations gene patterns, providing phenotypic diversity for act on....
ABSTRACT Heart valve cells mediate extracellular matrix (ECM) remodeling during postnatal leaflet stratification, but phenotypic and transcriptional diversity of in development is largely unknown. Single cell analysis mouse heart was used to evaluate heterogeneity ECM morphogenesis. The transcriptomic single from day (P)7 P30 murine aortic (AoV) mitral (MV) valves uncovered distinct subsets melanocytes, immune endothelial present at P7 P30. By contrast, interstitial populations are different...
Rationale: Lymphangioleiomyomatosis (LAM) is a metastatic neoplasm of reproductive-age women associated with mutations in tuberous sclerosis complex genes. LAM causes cystic remodeling the lung and progressive respiratory failure. The sources cellular characteristics cells underlying disease pathogenesis remain elusive.Objectives: Identification characterization human uterus using single-cell approach.Methods: Single-cell single-nuclei RNA sequencing on (n = 4) control 7) lungs,...
Abstract Examining kidney fibrosis is crucial for mechanistic understanding and developing targeted strategies against chronic disease (CKD). Persistent fibroblast activation tubular epithelial cell (TEC) injury are key CKD contributors. However, cellular transcriptional landscapes of specific activated clusters remain elusive. Here, we analyzed single transcriptomic profiles two clinically relevant models which induced robust parenchymal remodeling. We dissected the molecular stroma newly...
Development of vertebrate jaws involves patterning neural crest-derived mesenchyme cells into distinct subpopulations along the proximal-distal and oral-aboral axes. Although molecular mechanisms axis have been well studied, little is known regarding axis. Using unbiased single-cell RNA-seq analysis followed by in situ gene expression profiles, we show that Shh Bmp4 signaling pathways are activated a complementary pattern mouse embryonic mandibular arch. Tissue-specific inactivation hedgehog...
Abstract The urothelium is an epithelial barrier lining the bladder that protects against infection, fluid exchange and damage from toxins. nuclear receptor Pparg promotes urothelial differentiation in vitro, mutations are associated with cancer. However, function of healthy unknown. Here we show critical cells for mitochondrial biogenesis, cellular regulation inflammation response to urinary tract infection (UTI). Superficial cells, which maintaining barrier, fail mature mutants basal...
Different nephron tubule segments perform distinct physiological functions, collectively acting as a blood filtration unit. Dysfunction of the proximal segment can lead to Fanconi renotubular syndrome (FRTS), with major symptoms such excess excretion water, glucose, and phosphate in urine. It has been shown that mutation HNF4A is associated FRTS humans Hnf4a expressed specifically tubules adult rat nephrons. However, little known about role nephrogenesis. Here, we found both presumptive...
Abstract The uterus is a remarkable organ that must guard against infections while maintaining the ability to support growth of fetus without rejection. Hoxa10 and Hoxa11 genes have previously been shown play essential roles in development function. In this report we show Hoxa9,10,11 , Hoxc9,10,11, Hoxd9,10,11 redundant role formation uterine glands. addition, use single cell RNA-seq create high resolution gene expression atlas developing wild type mouse uterus. Cell types subtypes are...
The 39 mammalian Hox genes show problematic patterns of functional overlap. In order to more fully define the developmental roles it is necessary remove multiple combinations paralogous and flanking genes. addition, downstream molecular pathways regulated by during limb development remain incompletely delineated. this report we examine in mice with frameshift mutations six genes, Hoxa9,10,11 Hoxd9,10,11. were made a novel recombineering method that allows simultaneous targeting into −/−...
Abstract Persistent HPV16 infection is a major cause of the global cancer burden. The viral life cycle dependent on differentiation program stratified squamous epithelium, but landscape keratinocyte subpopulations which support distinct phases has yet to be elucidated. Here, single cell RNA sequencing infected compared uninfected organoids identifies twelve populations, with subset mapped reconstruct their respective 3D geography in epithelium. Instead conventional terminally differentiated...
Abstract Background The thin descending limb (DTL) of the loop Henle is crucial for urine concentration, as it facilitates passive water reabsorption. Despite its importance, little known about how DTL cells form during kidney development. Single-cell RNA sequencing (scRNA-seq) studies have not definitively identified in developing mouse kidney. Methods We assembled a large scRNA-seq dataset by integrating multiple datasets non-mutant kidneys to identify cells. To test whether originate from...
Intercellular transmission of messenger RNA (mRNA) is being explored in mammalian species using immortal cell lines. Here, we uncover an intercellular mRNA transfer phenomenon that allows for the adaptation and reprogramming human primed pluripotent stem cells (hPSCs). This process induced by direct contact-mediated coculture with mouse embryonic under condition impermissible hPSC culture. Mouse-derived contents are transmitted into adapted hPSCs only coculture. Transfer-specific analysis...
Cell proliferation is an elemental feature of epimorphic regeneration in vertebrate taxa. We previously reported that contrast to fibrotic repair observed laboratory mouse ( Mus ) strains, highly regenerative spiny mice Acomys spp.) exhibit cell cycle progression and faithfully replace missing tissue. However, little known about dynamics, specific types states may contribute complex tissue mammals. Using temporal pulse-chase experiments, we show stromal cells dimidiatus rapidly re-enter the...
Persistent infection with HPV causes nearly 5% of all cancers worldwide, including cervical and oropharyngeal cancers. Compared to HPV-negative (HPV−) head neck squamous cell carcinomas (HNSCCs), HPV-positive (HPV+) HNSCCs exhibit a significantly improved treatment response; however, established regimens were largely developed for HPV− disease. Effectively de-escalating therapy optimizing protocols minimize toxicity both HPV+ tumors has been variably successful, in part due the heterogeneity...
Hox genes are key regulators of development. In mammals, the study these is greatly confounded by their large number, overlapping functions and interspersed shared enhancers. Here, we describe use a novel recombineering strategy to introduce simultaneous frameshift mutations into flanking Hoxa9, Hoxa10 Hoxa11 genes, as well paralogs on HoxD cluster. The resulting Hoxa9,10,11 mutant mice displayed dramatic synergistic homeotic transformations reproductive tracts, with uterus anteriorized...