A5090138823- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- MicroRNA in disease regulation
- Congenital heart defects research
- Amyotrophic Lateral Sclerosis Research
- Extracellular vesicles in disease
- Alzheimer's disease research and treatments
- RNA Research and Splicing
Sanford Consortium for Regenerative Medicine
2023
University of California, San Diego
2023
University of California, San Francisco
2022
Interactions between angiogenesis and neurogenesis regulate embryonic brain development. However, a comprehensive understanding of the stages vascular cell maturation is lacking, especially in prenatal human brain. Using fluorescence-activated sorting, single-cell transcriptomics, histological ultrastructural analyses, we show that an ensemble endothelial mural subtypes tile vasculature during second trimester. These cells follow distinct developmental trajectories utilize diverse signaling...
Microglia phenotypes are highly regulated by the brain environment, but transcriptional networks that specify maturation of human microglia poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes fetal postnatal acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, cerebral organoids, following engraftment into humanized mice. Parallel development computational approaches considered transcription factor (TF)...
Mutations in the human Progranulin (GRN) gene are a leading cause of frontotemporal lobar degeneration (FTLD). While previous studies implicate aberrant microglial activation as disease-driving factor neurodegeneration thalamocortical circuit Grn-/- mice, exact mechanism for FTLD-GRN remains unclear. By performing comparative single-cell transcriptomics thalamus and frontal cortex mice patients with FTLD-GRN, we have uncovered highly conserved astroglial pathology characterized by...
The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in embryonic ventral forebrain. How this generates sufficient for brain remains unclear. We found that MGE (hMGE) nests of proliferative neuroblasts with ultrastructural and transcriptomic features distinguish them other progenitors hMGE. When dissociated hMGE cells are transplanted into neonatal mouse brain, they reform containing proliferating generate young neurons migrate...