A5080894389- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Genetic Mapping and Diversity in Plants and Animals
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Microtubule and mitosis dynamics
- Nerve injury and regeneration
- Single-cell and spatial transcriptomics
- Down syndrome and intellectual disability research
- Animal Genetics and Reproduction
- Peroxisome Proliferator-Activated Receptors
- Mesenchymal stem cell research
- Molecular Biology Techniques and Applications
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Neurogenesis and neuroplasticity mechanisms
- DNA Repair Mechanisms
- Drug Transport and Resistance Mechanisms
- Carcinogens and Genotoxicity Assessment
- Gene Regulatory Network Analysis
- Pediatric Hepatobiliary Diseases and Treatments
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- 3D Printing in Biomedical Research
Jackson Laboratory
2013-2024
Mount Desert Island Biological Laboratory
2007-2008
We report genome sequences of 17 inbred strains laboratory mice and identify almost ten times more variants than previously known. use these genomes to explore the phylogenetic history mouse examine functional consequences allele-specific variation on transcript abundance, revealing that at least 12% transcripts show a significant tissue-specific expression bias. By identifying candidate 718 quantitative trait loci we molecular nature their position relative genes vary according effect size...
We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. identify characterize 2,567 regions on the current reference exhibiting greatest sequence diversity. These are enriched genes involved in pathogen defence immunity exhibit enrichment of transposable elements signatures recent retrotransposition events. Combinations alleles unique to an individual strain commonly observed at these loci,...
Diverse inbred mouse strains are important biomedical research models, yet genome characterization of many is fundamentally lacking in comparison with humans. In particular, catalogs structural variants (SVs) (variants ≥ 50 bp) incomplete, limiting the discovery causative alleles for phenotypic variation. Here, we resolve genome-wide SVs 20 genetically distinct mice long-read sequencing. We report 413,758 site-specific affecting 13% (356 Mbp) reference assembly, including 510 previously...
Chromosome alignment at the equator of mitotic spindle is a highly conserved step during cell division; however, its importance to genomic stability and cellular fitness not understood. Normal mammalian somatic cells lacking KIF18A function complete division without aligning chromosomes. These alignment-deficient display normal chromosome copy numbers in vitro vivo, suggesting that largely dispensable for maintenance euploidy. However, we find loss leads interchromosomal compaction defects...
Variability among pluripotent stem cell (PSC) lines is a prevailing issue that hampers not only experimental reproducibility but also large-scale applications and personalized cell-based therapy. This variability could result from epigenetic genetic factors influence behavior. Naive culture conditions minimize fluctuation, potentially overcoming differences in PSC line differentiation potential. Here we derived PSCs distinct mouse strains under naive show backgrounds have divergent capacity,...
Abstract Neural progenitor cells (NPC) represent potential cell transplantation therapies for CNS injuries. To understand how lesion environments influence transplanted NPC fate in vivo, we derived expressing a ribosomal protein-hemagglutinin tag (RiboTag) transcriptional profiling of NPC. Here, show that grafted into uninjured mouse generate are transcriptionally similar to healthy astrocytes and oligodendrocyte lineages. In striking contrast, subacute lesions after stroke or spinal cord...
Spontaneously arising mouse mutations have served as the foundation for understanding gene function more than 100 years. We used exome sequencing in an effort to identify causative 172 distinct, spontaneously models of Mendelian disorders, including a broad range clinically relevant phenotypes. To analyze resulting data, we developed analytics pipeline that is optimized data and variation database allows reproducible, user-defined mining well nomination mutation candidates through...
The directed differentiation of pluripotent stem cells (PSCs) from panels genetically diverse individuals is emerging as a powerful experimental system for characterizing the impact natural genetic variation on developing cell types and tissues. Here, we establish new PSC lines approaches modeling embryonic development in diverse, outbred mouse stock (Diversity Outbred mice). We show that range inbred can be stably maintained primed state (epiblast -- EpiSCs) contribution to phenotypic...
Mouse embryonic stem (ES) cells are derived from the inner cell mass of blastocyst stage embryos and used primarily for creation genetically engineered strains through gene targeting. While some inbred mice permissive to derivation lines therefore easily engineered, others nonpermissive or recalcitrant. Genetic engineering recalcitrant strain backgrounds requires targeting in a background followed by extensive backcrossing allele into desired background. The mouse DBA/2J is that as model...
SUMMARY Diverse inbred mouse strains are among the foremost models for biomedical research, yet genome characterization of many has been fundamentally lacking in comparison to human genomics research. In particular, discovery and cataloging structural variants is incomplete, limiting potentially causative alleles phenotypic variation across individuals. Here, we utilized long-read sequencing resolve genome-wide (SVs, ≥ 50 bp) 20 genetically distinct mice. We report 413,758 site-specific SVs...
Abstract The most commonly employed mammalian model organism is the laboratory mouse. A wide variety of genetically diverse inbred mouse strains, representing distinct physiological states, disease susceptibilities, and biological mechanisms have been developed over last century. We report full length draft de novo genome assemblies for 16 widely used strains reveal first time extensive strain-specific haplotype variation. identify characterise 2,567 regions on current Genome Reference...
Mouse embryonic stem cells (mESCs) cultured under controlled conditions occupy a stable ground state where pluripotency-associated transcriptional and epigenetic circuitry are highly active. However, mESCs from some genetic backgrounds exhibit metastability, pluripotency is lost in the absence of ERK1/2 GSK3 inhibition. We dissected basis metastability by profiling gene expression chromatin accessibility 185 genetically heterogeneous mESCs. mapped thousands loci affecting and/or transcript...
The multidrug resistance-associated protein 3 (MRP3/Mrp3) is a member of the ATP-binding cassette (ABC) family membrane transporters and related proteins that act on variety xenobiotic anionic molecules to transfer these substrates in an ATP-dependent manner. In recent years, useful comparative information regarding evolutionarily conserved structure transport functions has accrued through use primitive marine animals such as cartilaginous fish. Until recently, one missing tool studies with...
SUMMARY Chromosome alignment at the equator of mitotic spindle is a highly conserved step during cell division, however, its importance to genomic stability and cellular fitness are not understood. Normal mammalian somatic cells lacking Kif18A function complete division without aligning chromosomes. These alignment-deficient display normal chromosome copy numbers in vitro vivo , suggesting that largely dispensable for maintenance euploidy. However, we find loss leads interchromosomal...