Marcus Hooper
A5036314434- Retinal Development and Disorders
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Advanced Fluorescence Microscopy Techniques
- RNA regulation and disease
- Advanced Electron Microscopy Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Glioma Diagnosis and Treatment
- Cell Image Analysis Techniques
- Force Microscopy Techniques and Applications
- Neuroscience and Neuropharmacology Research
- bioluminescence and chemiluminescence research
- Retinal Diseases and Treatments
- Immune cells in cancer
- Glaucoma and retinal disorders
- Retinal and Optic Conditions
- Adenosine and Purinergic Signaling
- Neural dynamics and brain function
- Machine Learning in Bioinformatics
- Retinopathy of Prematurity Studies
- Ocular Diseases and Behçet’s Syndrome
- Retinoids in leukemia and cellular processes
- Barrier Structure and Function Studies
Allen Institute for Brain Science
2023-2024
University of Washington
2019-2024
Allen Institute
2023-2024
University of Florida
2014-2018
University of Florida Health Science Center
2018
Pacific Northwest National Laboratory
1979
The mammalian brain consists of millions to billions cells that are organized into many cell types with specific spatial distribution patterns and structural functional properties1-3. Here we report a comprehensive high-resolution transcriptomic cell-type atlas for the whole adult mouse brain. was created by combining single-cell RNA-sequencing (scRNA-seq) dataset around 7 million profiled (approximately 4.0 passing quality control), approximately 4.3 using multiplexed error-robust...
Regenerative neuroscience aims to stimulate endogenous repair in the nervous system replace neurons lost from degenerative diseases. Recently, we reported that overexpressing transcription factor Ascl1 Müller glia (MG) is sufficient MG regenerate functional adult mouse retina. However, this process inefficient, and only a third of Ascl1-expressing generate new neurons. Here, test whether proneural factors Atoh1/7 class can further promote regenerative capacity MG. We find combination...
Müller glia (MG) serve as sources for retinal regeneration in non-mammalian vertebrates. We find that this process can be induced mouse MG, after injury, by transgenic expression of the proneural transcription factor Ascl1 and HDAC inhibitor TSA. However, new neurons are generated only from a subset MG. Identifying factors limit Ascl1-mediated MG reprogramming could make more efficient. In study, we test whether injury-induced STAT activation hampers ability to reprogram into neurons....
The innate immune system plays key roles in tissue regeneration. For example, microglia promote neurogenesis Müller glia birds and fish after injury. Although mammalian retina does not normally regenerate, can be induced mouse by Ascl1, a proneural transcription factor. We show that mice, inhibit the Ascl1-mediated retinal regeneration, suggesting limits regenerative response to
We previously used single-cell transcriptomic analysis to characterize human fetal retinal development and assessed the degree which organoids recapitulate normal development. now extend analyses incorporate assay for transposase-accessible chromatin sequencing (scATAC-seq), a powerful method potential gene regulatory networks through changes in accessible that accompany cell-state changes. The combination of scATAC-seq RNA (scRNA-seq) provides view developing retina at an unprecedented...
Many neurodegenerative diseases cause degeneration of specific types neurons. For example, glaucoma leads to death retinal ganglion cells, leaving other neurons intact. Neurons are not regenerated in the adult mammalian central nervous system. However, nonmammalian vertebrates, glial cells spontaneously reprogram into neural progenitors and replace after injury. We have recently developed strategies stimulate regeneration functional mouse retina by overexpressing proneural factor Ascl1...
The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution each cell type processes guided by essential for understanding its function in health and disease. We used transcriptomic epigenomic cortical taxonomies from mouse human define marker genes putative enhancers created a large toolkit transgenic lines enhancer AAVs selective targeting populations. report evaluation fifteen new driver lines, two reporter >800 different...
Müller glial cells (MG) generate retinal progenitor (RPC)-like after injury in non-mammalian species, though this does not occur the mammalian retina. Studies have profiled gene expression these to define genes that may be relevant their differences neurogenic potential. However, less is known about micro-RNA (miRNA) expression. In study, we compared miRNAs from RPCs and MG identify more highly expressed RPCs, others MG. To determine whether are difference potential between two cell types,...
Abstract Recent advances in tissue processing, labeling, and fluorescence microscopy are providing unprecedented views of the structure cells tissues at sub-diffraction resolutions near single molecule sensitivity, driving discoveries diverse fields biology, including neuroscience. Biological is organized over scales nanometers to centimeters. Harnessing molecular imaging across intact, three-dimensional samples on this scale requires new types microscopes with larger view working distance,...
Abstract Diseases and damage to the retina lead losses in retinal neurons eventual visual impairment. Although mammalian has no inherent regenerative capabilities, fish have robust regeneration from Müller glia (MG). Recently, we shown that driving expression of Ascl1 adult mouse MG stimulates neural regeneration. The observed is limited variety can be derived MG; -expressing primarily generate bipolar cells. To better understand limits MG-based retinas, used ATAC- RNA-seq compare newborn...
Recent advances in tissue processing, labeling, and fluorescence microscopy are providing unprecedented views of the structure cells tissues at sub-diffraction resolutions near single molecule sensitivity, driving discoveries diverse fields biology, including neuroscience. Biological is organized over scales nanometers to centimeters. Harnessing molecular imaging across intact, three-dimensional samples on this scale requires new types microscopes with larger view working distance, as well...
We present an enhancer AAV toolbox for accessing and perturbing striatal cell types circuits. Best-in-class vectors were curated major neuron populations including medium spiny neurons (MSNs), direct indirect pathway MSNs, as well Sst-Chodl, Pvalb-Pthlh, cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes virus delivery, with diverse transgene cargos. Importantly, we provide detailed information necessary to achieve reliable...
Identifying cell type-specific enhancers in the brain is critical to building genetic tools for investigating mammalian brain. Computational methods functional enhancer prediction have been proposed and validated fruit fly not yet We organized 'Brain Initiative Cell Census Network (BICCN) Challenge: Predicting Functional Type-Specific Enhancers from Cross-Species Multi-Omics' assess machine learning feature-based designed nominate DNA sequences target types mouse cortex. Methods were...
Retinal degeneration is a common cause of irreversible blindness and caused by the death retinal light-sensitive neurons called photoreceptors. At onset degeneration, stressed photoreceptors glial cells to secrete neuroprotective factors that slow pace degeneration. Leukemia inhibitory factor (LIF) one such required for endogenous neuroprotection. Photoreceptors are known release signals cellular stress, damage-associated molecular patterns (DAMPs) early in we hypothesized receptors DAMPs or...
Recent advances in tissue processing, labeling, and fluorescence microscopy are providing unprecedented views of the structure cells tissues at sub-diffraction resolutions near single molecule sensitivity, driving discoveries diverse fields biology, including neuroscience. Biological is organized over scales nanometers to centimeters. Harnessing molecular imaging across intact, three-dimensional samples on this scale requires new types microscopes with larger view working distance, as well...
Retinal degeneration in mammals causes permanent loss of vision, due to an inability regenerate naturally. Some non-mammalian vertebrates show robust regeneration, via Muller glia (MG). We have recently made significant progress stimulating adult mouse MG functional neurons by transgenic expression the proneural transcription factor Ascl1. While these results showed that can serve as endogenous source neuronal replacement, efficacy this process is limited. With goal improving mammals, we...
Retinal degeneration in mammals causes permanent loss of vision, due to an inability regenerate naturally. Some non-mammalian vertebrates show robust regeneration, via Muller glia (MG). We have recently made significant progress stimulating adult mouse MG functional neurons by transgenic expression the proneural transcription factor Ascl1. While these results showed that can serve as endogenous source neuronal replacement, efficacy this process is limited. With goal improving mammals, we...