A5012138144- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Nuclear Structure and Function
- Gene Regulatory Network Analysis
- Evolution and Genetic Dynamics
- Sepsis Diagnosis and Treatment
- Neurogenetic and Muscular Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Traumatic Brain Injury and Neurovascular Disturbances
- Plant Molecular Biology Research
- Acute Kidney Injury Research
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Signaling Pathways in Disease
- CRISPR and Genetic Engineering
European Molecular Biology Laboratory
2021-2023
European Molecular Biology Organization
2021-2022
Heidelberg University
2021-2022
Lund University
2017-2020
University of Chicago
2018-2020
Skåne University Hospital
2017
Drosophila melanogaster is a powerful, long-standing model for metazoan development and gene regulation. We profiled chromatin accessibility in almost 1 million expression half nuclei from overlapping windows spanning the entirety of embryogenesis. Leveraging developmental asynchronicity within embryo collections, we applied deep neural networks to infer age each nucleus, resulting continuous, multimodal views molecular cellular transitions absolute time. identify cell lineages; their...
Abstract Enhancers control gene expression and have crucial roles in development homeostasis 1–3 . However, the targeted de novo design of enhancers with tissue-specific activities has remained challenging. Here we combine deep learning transfer to for five tissues Drosophila melanogaster embryo: central nervous system, epidermis, gut, muscle brain. We first train convolutional neural networks using genome-wide single-cell assay transposase-accessible chromatin sequencing (ATAC-seq) datasets...
Sepsis-induced acute kidney injury (AKI) is a common condition with high morbidity and mortality. Neutrophil-derived heparin-binding protein (HBP) induces vascular leakage promising biomarker of sepsis-induced organ dysfunction. It remains unknown if HBP prognostic AKI in septic shock could play role the pathophysiology AKI.To determine association plasma levels development AKI, investigate test effect blocking using heparin derivatives.In 296 patients from randomized multicenter Vasopressin...
Abstract While it is established that the functional impact of genetic variation can vary across cell types and states, capturing this diversity remains challenging. Current studies using bulk sequencing either ignore heterogeneity or use sorted populations, reducing discovery explanatory power. Here, we develop scDALI, a versatile computational framework integrates information on cellular states with allelic quantifications single-cell data to characterize cell-state-specific effects. We...
Developmental progression and cellular diversity are largely driven by transcription factors (TFs); yet, characterizing their loss-of-function phenotypes remains challenging often disconnected from underlying molecular mechanisms. Here, we combine single-cell regulatory genomics with mutants to jointly assess both phenotypes. Performing sci-ATAC-seq at eight overlapping time points during Drosophila mesoderm development could reconstruct the developmental trajectories of all major muscle...
Nutrient deprivation induces a reversible cell cycle arrest state termed quiescence, which often accompanies transcriptional silencing and chromatin compaction. Paradoxically, nutrient is associated with activated fibroblast states in pathological microenvironments fibroblasts drive extracellular matrix (ECM) remodeling to alter tissue environments. The relationship between activation remains unclear. Here, we report that serum extensively activates transcription of ECM genes cultured...
ABSTRACT The nuclear envelope, a defining feature of eukaryotic cells, restricts DNA-dependent processes including gene transcription to the nucleus. lamina is an integral component animal composed polymers lamin proteins 1,2 . Upon mitosis, disassembles, envelope breaks down, and becomes quiescent 3,4 We report here direct molecular link between disassembly mitotic transcriptional quiescence. found that, at G2 cell-cycle phase immediately preceding A/C (LMNA) became phosphorylated Ser22...
ABSTRACT LMNA encodes nuclear lamin A/C that tethers lamina-associated heterochromatin domains (LADs) to the periphery. Point mutations in cause degenerative disorders including premature aging disorder Hutchinson-Gilford progeria, but mechanisms are unknown. We report Ser22-phosphorylated Lamin (pS22-Lamin A/C) was localized interior of nucleus human fibroblasts throughout cell cycle. pS22-Lamin interacted with a specific subset putative active enhancers, not LADs, primarily at locations...
Abstract While the functional impact of genetic variation can vary across cell types and states, capturing this diversity remains challenging. Current studies, using bulk sequencing, ignore much heterogeneity, reducing discovery explanatory power. Single-cell approaches combined with F1 designs provide a new opportunity to address problem, however suitable computational methods model these complex relationships are lacking. Here, we developed scDALI, an analysis framework that integrates...
The nuclear lamina, composed of polymers lamins, maintains the structural integrity animal nuclei and tethers heterochromatin to periphery. Lamins depolymerize upon envelope breakdown at mitosis, however, no specific functions for depolymerized lamins have been described. We show that Lamin A/C (dLMNA) links mitotic transcriptional quiescence in human fibroblasts. dLMNA was Ser22-phosphorylated released interior during G2, immediately preceeding mitosis. bound active promoters enhancers...
The segregation of heterochromatin domains (LADs) at the nuclear periphery by lamina, composed polymerized Lamin A/C, provides a longstanding paradigm for control gene expression and mechanisms underlying Lamin-A/C-associated disorders, including progeria cardiomyopathy. Here, we provide evidence supporting novel that A/C functions as transcription factor in interior. We discovered Ser22-phosphorylated (pS22-Lamin A/C), required lamin depolymerization during mitosis, populated interior...