A5048140711- Single-cell and spatial transcriptomics
- Advanced Fluorescence Microscopy Techniques
- Pluripotent Stem Cells Research
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammasome and immune disorders
- Congenital heart defects research
- Advanced biosensing and bioanalysis techniques
- Immune responses and vaccinations
- Genomics and Chromatin Dynamics
- Image Processing Techniques and Applications
- Adenosine and Purinergic Signaling
- RNA modifications and cancer
- Photoacoustic and Ultrasonic Imaging
- Renal and related cancers
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Molecular Biology Techniques and Applications
- Biosensors and Analytical Detection
- Reproductive System and Pregnancy
- Genetic Syndromes and Imprinting
University of Washington
2020-2025
University of California, Berkeley
2019-2021
Abstract The house mouse ( Mus musculus ) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans 1,2 . Mouse gestation lasts only 3 weeks, during which the genome orchestrates astonishing transformation of a single-cell zygote into free-living pup composed more than 500 million cells. Here, establish global framework for exploring mammalian development, we applied optimized combinatorial indexing profile transcriptional states 12.4 nuclei...
Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction live imaging a biological sample within timeframe interest. Here we demonstrate an alternative paradigm in which such activities stably recorded to genome. Enhancer-driven genomic recording transcriptional multiplex (ENGRAM) is based on signal-dependent production prime editing guide RNAs mediate insertion signal-specific barcodes (symbols) into...
Abstract Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed all three germ layers, gastruloids do not morphologically resemble post-implantation embryos. Here we show that an pulse retinoic acid (RA), together with later Matrigel, robustly induces posterior embryo-like morphological structures, including neural tube flanked by segmented somites diverse cell types, crest, progenitors, renal progenitors myocytes. Through silico...
Abstract The house mouse, Mus musculus , is an exceptional model system, combining genetic tractability with close homology to human biology. Gestation in mouse development lasts just under three weeks, a period during which its genome orchestrates the astonishing transformation of single cell zygote into free-living pup composed >500 million cells. Towards global framework for exploring mammalian development, we applied combinatorial indexing (sci-*) profile transcriptional states 12.4...
Single-cell genomics methods have unveiled the heterogeneity present in seemingly homogenous populations of cells, however, these techniques require meticulous optimization. How exactly does one handle and manipulate biological contents from a single cell? Here, we introduce characterize novel semi-permeable capsule (SPC), capable isolating cells their while facilitating biomolecular exchange based on size-selectivity. These capsules maintain stability under diverse physical chemical...
The cell cycle governs the proliferation of all eukaryotic cells. Profiling dynamics is therefore central to basic and biomedical research. However, current approaches profiling involve complex interventions that may confound experimental interpretation. We developed CellCycleNet, a machine learning (ML) workflow, simplify staging from fluorescent microscopy data with minimal experimenter intervention cost. CellCycleNet accurately predicts phase using only nuclear stain (DAPI) in fixed...
Abstract Measurements of gene expression and signal transduction activity are conventionally performed with methods that require either the destruction or live imaging a biological sample within timeframe interest. Here we demonstrate an alternative paradigm, termed ENGRAM ( EN hancer-driven G enomic R ecording transcriptional A ctivity in M ultiplex), which dynamics multiple reporters stably recorded to DNA. is based on prime editing-mediated insertion signal- enhancer-specific barcodes...
ABSTRACT Embryonic organoids are emerging as powerful models for studying early mammalian development. For example, stem cell-derived ‘gastruloids’ form elongating structures containing all three germ layers 1–4 . However, although elongated, human gastruloids do not morphologically resemble post-implantation embryos. Here we show that a specific, discontinuous regimen of retinoic acid (RA) robustly induces with embryo-like morphological structures, including neural tube and segmented...
Abstract In situ hybridization (ISH) is a powerful tool for investigating the spatial arrangement of nucleic acid targets in fixed samples. ISH typically visualized using fluorophores to allow high sensitivity and multiplexing or with colorimetric labels facilitate co-visualization histopathological stains. Both approaches benefit from signal amplification, which makes target detection effective, rapid, compatible broad range optical systems. Here, we introduce unified technical platform,...
Abstract Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need user-friendly system that can address applications with varied requirements in terms resolution (mesoscopic to sub-micrometer), sample geometry (size, shape, and number), compatibility tissue-clearing protocols holders various refractive indices. We present ‘hybrid’ combines novel non-orthogonal dual-objective conventional (orthogonal)...
Abstract Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need user-friendly system that can address applications with varied requirements in terms resolution (mesoscopic to sub-micrometer), sample geometry (size, shape, and number), compatibility tissue-clearing protocols holders various refractive indices. We present ‘hybrid’ combines novel non-orthogonal dual-objective conventional (orthogonal)...
The cell cycle governs the proliferation, differentiation, and regeneration of all eukaryotic cells. Profiling dynamics is therefore central to basic biomedical research spanning development, health, aging, disease. However, current approaches profiling involve complex interventions that may confound experimental interpretation. To facilitate more efficient annotation microscopy data, we developed CellCycleNet, a machine learning (ML) workflow designed simplify staging with minimal...
Summary Maternal immune activation (MIA) increases likelihood of altered neurodevelopmental outcomes. cytokines are proposed to affect fetal brain development in mice; however, the contribution immunity disorders is largely unexplored. Here, we show that MIA mediated by Toll-like receptor 3 (TLR3), but not other TLRs, induces a specific set behavioral phenotypes including decreased sociability and increased restricted repetitive behavior offspring. Accordingly, these were absent when...
Microglial cells are known to contribute brain development and behaviors, but the mechanisms behind such functions not fully understood. Here, we show that mice deficient in inflammasome regulators, including caspase-1 (Casp1), NLR family pyrin domain containing 3 (Nlrp3), IL-1 receptor (Il-1r), gasdermin D (Gsdmd), exhibit behavior abnormalities characterized by hyperactivity low anxiety levels. Furthermore, found expression of Casp1 CX3CR1+ myeloid cells, which includes microglia, is...
Microglia are resident immune cells in the central nervous system that play essential roles to maintain homeostasis and neuronal function. heterogeneous but mechanisms by which they contribute normal brain development remain unclear. Here,we show microglia developing striatum thalamus undergo pyroptosis,a type of lytic cell death occurs as a result Caspase-1 (CASP1) activation downstream inflammasomes. We observe pyroptosis spatiotemporally regulated Casp1-dependent manner during fetal...
<title>Abstract</title> Measurements of gene expression and signal transduction activity are conventionally performed with methods that require either the destruction or live imaging a biological sample within timeframe interest. Here we demonstrate an alternative paradigm, termed ENGRAM (ENhancer-driven Genomic Recording transcriptional Activity in Multiplex), which dynamics multiple reporters stably recorded to DNA. is based on prime editing-mediated insertion signal- enhancer-specific...