A5035164294- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Congenital heart defects research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Pluripotent Stem Cells Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- Gene expression and cancer classification
- Ubiquitin and proteasome pathways
- Bioinformatics and Genomic Networks
- Chromosomal and Genetic Variations
- BRCA gene mutations in cancer
- Microtubule and mitosis dynamics
- Peroxisome Proliferator-Activated Receptors
- Zebrafish Biomedical Research Applications
- Acute Myeloid Leukemia Research
- Genomics and Rare Diseases
- Evolution and Genetic Dynamics
- Genomic variations and chromosomal abnormalities
- Cell Image Analysis Techniques
- Plant Molecular Biology Research
University of Washington
2018-2024
Seattle University
2020-2022
Baylor College of Medicine
2017-2020
Rice University
2017-2020
Applied Mathematics (United States)
2017-2020
Center for Theoretical Biological Physics
2019-2020
Eukaryotic genomes are folded into loops. It is thought that these formed by cohesin complexes
Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, single-cell zygote gives rise to millions of cells expressing panoply molecular programs. Although intensively studied, comprehensive delineation the major trajectories that comprise mammalian development in vivo remains elusive. Here, we set out integrate several RNA-sequencing (scRNA-seq) datasets collectively span mouse gastrulation organogenesis, supplemented with new...
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 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...
Cataloging the diverse cellular architecture of primate brain is crucial for understanding cognition, behavior, and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas rhesus macaque brain. Together, profiled 2.58 M transcriptomes 1.59 epigenomes from single nuclei sampled 30 regions across adult Cell composition differed extensively brain, revealing signatures region-specific functions. We also identified 1.19 candidate regulatory elements, many...
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...
Abstract Mouse models are a critical tool for studying human diseases, particularly developmental disorders 1 . However, conventional approaches phenotyping may fail to detect subtle defects throughout the developing mouse 2 Here we set out establish single-cell RNA sequencing of whole embryo as scalable platform systematic genetic models. We applied combinatorial indexing-based 3 profile 101 embryos 22 mutant and 4 wild-type genotypes at embryonic day 13.5, altogether profiling more than...
Abstract Spinal cord injury (SCI) remains one of the most debilitating neurological disorders and majority SCI patients are in chronic phase. Previous studies have usually focused on few genes pathways at a time. In particular, biological roles long non-coding RNAs (lncRNAs) never been characterized SCI. Our study is first to comprehensively investigate alterations expression both coding sub-chronic stages using RNA-Sequencing. Through pathway analysis network construction, functions...
The human genome folds in 3 dimensions to form thousands of chromatin loops inside the nucleus, encasing genes and cis-regulatory elements for accurate gene expression control. Physical tethers are anchored by DNA-binding protein CTCF cohesin ring complex. Because heart failure is characterized hallmark changes, it was recently reported that substantial CTCF-related reorganization underpins myocardial stress-gene response, paralleled domain boundary changes observed knockout.We undertook an...
SUMMARY The human genome folds to create thousands of intervals, called “contact domains,” that exhibit enhanced contact frequency within themselves. “Loop domains” form because tethering between two loci - almost always bound by CTCF and cohesin – lying on the same chromosome. “Compartment when genomic intervals with similar histone marks co-segregate. Here, we explore effects degrading cohesin. All loop domains are eliminated, but neither compartment nor affected. Loci in different...
Abstract Variants of uncertain significance (VUS) fundamentally limit the utility genetic information in a clinical setting. The challenge VUS is epitomized by BRCA1 , tumor suppressor gene integral to DNA repair and genomic stability. Germline loss-of-function (LOF) variants predispose women early-onset breast ovarian cancers. Although has been sequenced millions women, risk associated with most newly observed cannot be definitively assigned. Data sharing attenuates this problem but it...
Abstract Higher order chromatin structure and DNA methylation are implicated in multiple developmental processes, but their relationship to cell state is unknown. Here, we found that large (~10kb) nadirs can form long loops connecting anchor loci may be dozens of megabases apart, as well interchromosomal links. The interacting comprise ~3.5Mb the human genome. data more consistent with formation these by phase separation a genomic subcompartment, rather than CTCF-mediated extrusion....
Abstract Mouse models are a critical tool for studying human diseases, particularly developmental disorders, as well advancing our general understanding of mammalian biology. However, it has long been suspected that conventional approaches phenotyping insufficiently sensitive to detect subtle defects throughout the developing mouse. Here we set out establish single cell RNA sequencing (sc-RNA-seq) whole embryo scalable platform systematic molecular and cellular mouse genetic models. We...
Abstract Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, single cell zygote gives rise to millions of cells expressing panoply molecular programs, including much the diversity that will subsequently be present in adult tissues. Although intensively studied, comprehensive delineation major trajectories comprise mammalian development vivo remains elusive. Here we set out integrate several RNA-seq datasets (scRNA-seq)...
Abstract Eukaryotic genomes are folded into loops. It is thought that these formed by cohesin complexes via extrusion, either until loop expansion arrested CTCF or removed from DNA WAPL. Although WAPL limits cohesin’s chromatin residence time to minutes, it has been reported some loops exist for hours. How can persist unknown. We show during G1-phase, mammalian cells contain acetylated STAG1 which binds hours, whereas STAG2 minutes. Our results indicate and the acetyltransferase ESCO1...
Abstract Cataloging the diverse cellular architecture of primate brain is crucial for understanding cognition, behavior and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas rhesus macaque brain. Altogether, profiled 2.58M transcriptomes 1.59M epigenomes from single nuclei sampled 30 regions across adult Cell composition differed extensively brain, revealing signatures region-specific functions. We also identified 1.19M candidate regulatory elements,...