Microglia play important roles in developmental and homeostatic brain function, and influence the establishment and progression of many neurological disorders. Here, we demonstrate that renewable human iPSCs can be efficiently differentiated to microglial-like cells (iMGL) to study neurological diseases, such as Alzheimer''s disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo and whole transcriptome analysis demonstrates that they are highly similar to adult and fetal human microglia. Functional assessment of iMGLs reveal that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. We also show novel use of iMGLs to examine the effects of fibrillar Aß and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Taken together, these findings demonstrate that iMGLs can be used in high-throughput studies of microglial function, providing important new insight into human neurological disease. Overall design: Human cells were collected and analyzed for gene expression using RNA-seq.
iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
Specimen part, Subject
View SamplesMidbrain dopaminergic (mDA) neurons degenerate in Parkinson's disease and are one of the main targets for cell replacement therapies. A comprehensive view of the signals and cell types contributing to mDA neurogenesis is not yet available. By analyzing the transcriptome of the mouse ventral midbrain at tissue and single-cell level during mDA neurogenesis we found that three recently identified radial glia types (Rgl 1-3) contribute to different key aspects of mDA neurogenesis. While Rgl3 expressed most extracellular matrix components and multiple ligands for various pathways controlling mDA neuron development, such as Wnt and Shh, Rgl1-2 expressed most receptors. Moreover, we found that specific transcription factor networks explain the transcriptome expression profiles and suggest a function for each individual radial glia type. Overall design: Triplicate tissue samples from each combination of embryonic day E11.5, E12.5, E13.5, and E14.5 with brain region alar plate, dorsal midbrain, ventral forebrain, ventral hindbrain, and ventral midbrain.
The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation.
Specimen part, Subject
View SamplesInvestigations into the roles for Pbx1 and its transcriptional network in dopaminergic neuron development and Parkinson's Disease Overall design: Three samples each from dorsal midbrain, forebrain, hindbrain, Alar plate, and ventral midbrain
The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation.
Cell line, Subject
View Samples5069 transcriptomes of single oligodendrocyte cells from spinal cord, substantia nigra-ventral tegmental area, striatum, amygdala, hypothalamic nuclei, zona incerta, hippocampus, and somatosensory cortex of male and female mice between post-natal day 21 and 90. The study aimed at identifying diverse populations of oligodendrocytes, and revealing dynamics of oligodendrocyte maturation. Overall design: 5069 individual cells were sampled from CNS regions of mice of various strains as detailed in the protocols section
Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system.
Sex, Cell line, Treatment, Subject
View Samples