A5054139228- Single-cell and spatial transcriptomics
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Gene Regulatory Network Analysis
- Computational Drug Discovery Methods
- Genetic factors in colorectal cancer
- Pluripotent Stem Cells Research
- Genetics, Bioinformatics, and Biomedical Research
- Genomics and Rare Diseases
- Genomics and Chromatin Dynamics
Yale University
2020-2023
University of Connecticut
2018-2021
Mosaic mutations can be used to track cell lineages in humans. We cloning analyze embryonic two living individuals and a postmortem human specimen. Of 10 reconstructed postzygotic divisions, none resulted balanced contributions of daughter tissues. In both individuals, one from the first cleavage was dominant across tissues, with 90% frequency blood. propose that efficiency DNA repair contributes lineage imbalance. Allocation brain correlated anterior-posterior axis, associating history fate...
Summary There is no clear genetic etiology or convergent pathophysiology for autism spectrum disorders (ASD). Using cortical organoids and single-cell transcriptomics, we modeled alterations in the formation of forebrain between sons with idiopathic ASD their unaffected fathers thirteen families. Alterations transcriptome suggest that pathogenesis macrocephalic normocephalic probands involves an opposite disruption balance excitatory neurons dorsal plate other lineages such as...
Abstract Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurogenetic disorder caused by duplications of the maternal copy this region. In addition to hypotonia, motor deficits, and language impairments, Dup15q patients commonly meet criteria for autism spectrum (ASD) have high prevalence seizures. Here, we explored mechanisms hyperexcitability in neurons derived from induced pluripotent stem cell (iPSC) lines patients. Maturation resting membrane potential Dup15q-derived was similar...
Abstract Mosaic mutations can be used to track cell ancestries and reconstruct high-resolution lineage trees during cancer progression development, starting from the first divisions of zygote. However, this approach requires sampling analyzing genomes multiple cells, which redundant in representation, limiting scalability approach. We describe a strategy for cost- time-efficient reconstruction using clonal induced pluripotent stem lines human skin fibroblasts. The leverages shallow...
Abstract Post-zygotic mosaic mutations can be used to track cell lineages in humans. By using cloning and induced pluripotent lines, we analyzed early two living individuals (a patient a control), postmortem human specimen. Of ten reconstructed post-zygotic divisions, none resulted balanced contributions of daughter tissues. In both one from the first cleavage was dominant across tissues, with 90% frequency blood. We propose that efficiency DNA repair contributes lineage imbalance....
Abstract Cell differentiation involves shifts in chromatin organization allowing transcription factors (TFs) to bind enhancer elements and modulate gene expression. The TF-enhancer-gene regulatory interactions that control the formation of neuronal lineages have yet be charted humans. Here, we mapped conducted an integrative analysis epigenomic transcriptomic profiles across 60 days human forebrain organoids derived from 10 individuals with autism spectrum disorder (ASD) their neurotypical...