A5001921760- Muscle Physiology and Disorders
- Gene Regulatory Network Analysis
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Long-Term Effects of COVID-19
- Neonatal Respiratory Health Research
- Exercise and Physiological Responses
- Nutrition and Health in Aging
- Circadian rhythm and melatonin
- Estrogen and related hormone effects
- Cancer, Stress, Anesthesia, and Immune Response
- Genetic Neurodegenerative Diseases
- Tissue Engineering and Regenerative Medicine
- Cancer Cells and Metastasis
- Genetics and Physical Performance
- MicroRNA in disease regulation
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Adipokines, Inflammation, and Metabolic Diseases
- Immunotherapy and Immune Responses
- Metabolomics and Mass Spectrometry Studies
- Zebrafish Biomedical Research Applications
Washington University in St. Louis
2017-2024
Pulmonary and Critical Care Associates
2021
Max Planck Society
2012
Max Planck Institute of Biochemistry
2012
Abstract Cell identity is governed by the complex regulation of gene expression, represented as gene-regulatory networks 1 . Here we use inferred from single-cell multi-omics data to perform in silico transcription factor perturbations, simulating consequent changes cell using only unperturbed wild-type data. We apply this machine-learning-based approach, CellOracle, well-established paradigms—mouse and human haematopoiesis, zebrafish embryogenesis—and correctly model reported phenotype that...
Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout day. These methods hold significant promise for future discovery, when combined with computational modeling. However, genome-scale experiments are costly laborious, yielding “big data” that conceptually statistically difficult analyze. There is no obvious consensus...
Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively certain groups. These observations suggest that factors intrinsic to influence their resistance disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq profile mRNA expression in skeletal, smooth,...
Summary Here, we present CellOracle, a computational tool that integrates single-cell transcriptome and epigenome profiles to infer gene regulatory networks (GRNs), critical regulators of cell identity. Leveraging inferred GRNs, simulate expression changes in response transcription factor (TF) perturbation, enabling network configurations be interrogated silico , facilitating their interpretation. We validate the efficacy CellOracle recapitulate known across hematopoiesis, correctly...
Epithelial cells are charged with protection at barrier sites, but whether this normally beneficial response might sometimes become dysfunctional still needs definition. Here, we recognized a pattern of imbalance marked by basal epithelial cell growth and differentiation that replaced normal airspaces in mouse model progressive postviral lung disease due to the Sendai virus. Single-cell lineage-tracing technologies identified distinct subset stem (basal ESCs) extended into gas-exchange...
In direct lineage conversion, transcription factor (TF) overexpression reconfigures gene regulatory networks (GRNs) to reprogram cell identity. We previously developed CellOracle, a computational method infer GRNs from single-cell transcriptome and epigenome data. Using inferred GRNs, CellOracle simulates expression changes in response TF perturbation, enabling silico interrogation of network reconfiguration. Here, we combine analysis with tracing fibroblast induced endoderm progenitor (iEP)...
Epithelial barriers are programmed for defense and repair but also the site of long-term structural remodeling disease. In general, this paradigm features epithelial stem cells (ESCs) that called on to regenerate damaged tissues can be reprogrammed detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population functioned as an early sentinel niche basal ESC reprogramming in mouse models injury after respiratory viral infection. Niche function...
Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased mass in turn lowered physical activity survival rates. Previous models atrophy chronic modeled obstructive pulmonary (COPD) relied on cigarette smoke exposure LPS stimulation, but these conditions independently affect even without accompanying disease. there an emerging pressing need to...
Abstract Skeletal muscle comprises a family of diverse tissues with highly specialized morphology, function, and metabolism. Many acquired diseases – including HIV, COPD, cancer cachexia, critical illness myopathy, sepsis affect specific muscles while sparing others. Even monogenic muscular dystrophies tend to selectively certain groups, despite their causative genetic mutations being present in all tissues. These observations suggest that factors intrinsic influence susceptibility various...
Summary In direct lineage reprogramming, transcription factor (TF) overexpression reconfigures Gene Regulatory Networks (GRNs) to convert cell identities between fully differentiated types. We previously developed CellOracle, a computational pipeline that integrates single-cell transcriptome and epigenome profiles infer GRNs. CellOracle leverages these inferred GRNs simulate gene expression changes in response TF perturbation, enabling network re-configuration during reprogramming be...
Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased mass in turn lowered physical activity survival rates. Previous models atrophy chronic modeled COPD relied on cigarette smoke exposure LPS-stimulation, but these conditions independently affect even without accompanying disease. there an emerging pressing need to understand manifestations...
TGFβ plays an important role in skeletal muscle by inhibiting cell differentiation and regulating inflammation extracellular matrix production. Recent data link with reduced expression of mitochondrial regulators, key regulators β-oxidation, negative influence on insulin response, providing a potential mechanism for exercise non-response.
Skeletal muscle comprises a family of diverse tissues with highly specialized morphology, function, and metabolism. Many acquired diseases – including HIV, COPD, cancer cachexia, critical illness myopathy, sepsis affect specific muscles while sparing others. Even monogenic muscular dystrophies tend to selectively certain groups, despite their causative genetic mutations being present in all tissues. These observations suggest that factors intrinsic influence susceptibility various disease...