- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- Axon Guidance and Neuronal Signaling
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Cell Image Analysis Techniques
- Neuroscience and Neural Engineering
- Neural dynamics and brain function
- Nerve injury and regeneration
- 3D Printing in Biomedical Research
- Neuroscience, Education and Cognitive Function
- MicroRNA in disease regulation
- RNA modifications and cancer
- Photoreceptor and optogenetics research
- bioluminescence and chemiluminescence research
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Zebrafish Biomedical Research Applications
- Biomedical Ethics and Regulation
- Cancer-related molecular mechanisms research
- Gene Regulatory Network Analysis
- Genetics and Neurodevelopmental Disorders
Harvard University
2015-2024
Broad Institute
2015-2024
Harvard University Press
2007-2024
University of California, San Francisco
2024
Salk Institute for Biological Studies
2023
Massachusetts General Hospital
2003-2020
University of Padua
2019
Harvard Stem Cell Institute
2005-2017
Boston University
2006
Boston Children's Hospital
2003
Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested in vivo relevance through genetic ablation animal models. To investigate the of lncRNAs various physiological conditions, we developed a collection 18 lncRNA knockout strains which locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes three mutant (Fendrr, Peril, Mdgt), latter two exhibiting incomplete penetrance growth...
Myelin is a defining feature of the vertebrate nervous system. Variability in thickness myelin envelope structural affecting conduction neuronal signals. Conversely, distribution myelinated tracts along length axons has been assumed to be uniform. Here, we traced high-throughput electron microscopy reconstructions single pyramidal neurons mouse neocortex and built high-resolution maps myelination. We find that individual have distinct longitudinal myelin. Neurons superficial layers displayed...
Striatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntington's disease. We find that the transcription factor Ctip2 (also known as Bcl11b ) central to MSN differentiation striatal development. Within striatum, it expressed by all MSN, although excluded from essentially interneurons. In absence , do not fully differentiate, demonstrated dramatically reduced expression large number markers, including DARPP-32,...
The number of disease risk genes and loci identified through human genetic studies far outstrips the capacity to systematically study their functions. We applied a scalable screening approach, in vivo Perturb-Seq, functionally evaluate 35 autism spectrum disorder/neurodevelopmental delay (ASD/ND) de novo loss-of-function genes. Using CRISPR-Cas9, we introduced frameshift mutations these pools, within developing mouse brain utero, followed by single-cell RNA-sequencing perturbed cells...
Transcription factor programming of pluripotent stem cells (PSCs) has emerged as an approach to generate human neurons for disease modeling. However, schemes produce a variety cell types, and those that are made often retain immature phenotype, which limits their utility in modeling neuronal processes, including synaptic transmission. We report combining NGN2 with SMAD WNT inhibition generates patterned induced (hpiNs). Single-cell analyses showed hpiN cultures contained along developmental...
Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels cerebral cortex