A5077155003- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Immune cells in cancer
- Neuroscience and Neuropharmacology Research
- IL-33, ST2, and ILC Pathways
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Pluripotent Stem Cells Research
- Zebrafish Biomedical Research Applications
- Immune Response and Inflammation
- Phagocytosis and Immune Regulation
- Tryptophan and brain disorders
- Gene expression and cancer classification
- Advanced Fluorescence Microscopy Techniques
- Bioinformatics and Genomic Networks
- interferon and immune responses
- MicroRNA in disease regulation
- Calcium signaling and nucleotide metabolism
- Single-cell and spatial transcriptomics
- Reproductive System and Pregnancy
- Pain Mechanisms and Treatments
- Genetics and Neurodevelopmental Disorders
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Neonatal and fetal brain pathology
University of California, San Francisco
2015-2025
Broad Center
2012-2024
University of San Francisco
2024
University of Warsaw
2020
Universidad Católica de Santa Fe
2018
Howard Hughes Medical Institute
2004-2014
Broad Institute
2014
Langley Porter Psychiatric Hospital and Clinics
2012-2013
University of Michigan–Ann Arbor
2003-2006
Bmi-1 is required for the post-natal maintenance of stem cells in multiple tissues including central nervous system (CNS) and peripheral (PNS). Deletion Ink4a or Arf from -/- mice partially rescued cell self-renewal frequency CNS PNS, as well forebrain proliferation gut neurogenesis. deficiency, but not cerebellum development, demonstrating regional differences sensitivity progenitors to p16 p19 . both did affect growth survival completely rescue neural development. thus prevents premature...
Call to action The developing brain initially makes more synapses than it needs. With further development, excess are pruned away, leaving mature circuits. Synapses can be eliminated by microglia, which engulf and destroy them. Vainchtein et al. found that the microglia called into astrocytes, supportive cells on neurons rely. Astrocytes near a redundant synapse release cytokine interleukin-33 (IL-33), recruits site. In mice, disruptions in this process, as caused deficiency IL-33, led too...
Astrocytes, the most abundant cell population in central nervous system (CNS), are essential for normal neurological function. We show that astrocytes allocated to spatial domains mouse spinal cord and brain accordance with their embryonic sites of origin ventricular zone. These remain stable throughout life without evidence secondary tangential migration, even after acute CNS injury. Domain-specific depletion ventral resulted abnormal motor neuron synaptogenesis, which was not rescued by...
Microglia are brain-resident macrophages that shape neural circuit development and implicated in neurodevelopmental diseases. Multiple microglial transcriptional states have been defined, but their functional significance is unclear. Here, we identify a type I interferon (IFN-I)-responsive state the developing somatosensory cortex (postnatal day 5) actively engulfing whole neurons. This population expands during cortical remodeling induced by partial whisker deprivation. Global or...
Expansion of astrocyte populations in the central nervous system is characteristic evolutionarily more complex organisms. However, regulation mammalian precursor proliferation during development remains poorly understood. Here, we used Aldh1L1-GFP to identify two morphologically distinct types proliferative precursors: radial glia (RG) ventricular zone and a second cell type call an ‘intermediate precursor’ (IAP) located mantle region spinal cord. Astrogenic RG IAP cells proliferated...
Diversified neurons are essential for sensorimotor function, but whether astrocytes become specialized to optimize circuit performance remains unclear. Large fast α-motor (FαMNs) of spinal cord innervate fast-twitch muscles that generate peak strength. We report ventral horn express the inward-rectifying K+ channel Kir4.1 (a.k.a. Kcnj10) around MNs in a VGLUT1-dependent manner. Loss astrocyte-encoded selectively altered FαMN size and function led reduced Overexpression was sufficient...
Peripheral nerve injury-induced neuropathic pain is a chronic and debilitating condition characterized by mechanical hypersensitivity. We previously identified microglial activation via release of colony-stimulating factor 1 (CSF1) from injured sensory neurons as mechanism contributing to pain. Here, we show that intrathecal administration CSF1, even in the absence injury, sufficient induce behavior, but only male mice. Transcriptional profiling morphologic analyses after CSF1 showed robust...
Lysosomes are important sites for macromolecular degradation, defined by an acidic lumenal pH of ∼4.5. To better understand lysosomal pH, we designed a novel, genetically encoded, fluorescent protein (FP)-based biosensor called Fluorescence Indicator REporting in (FIRE-pHLy). This was targeted to lysosomes with lysosomal-associated membrane 1 (LAMP1) and reported between 3.5 6.0 monomeric teal (mTFP1), bright cyan pH-sensitive FP variant pKa 4.3. Ratiometric quantification enabled...
The brain's resident macrophages have many roles beyond synaptic pruning.