Project description:Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABAA channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1.
Project description:In this dataset, we studied human dopaminergic neuron differenation from induced pluripotent stem cells (iPSCs). We included the gene expression data obtained from iPSCs and iPSC-derived dopaminergic neurons. This dataset is used to predict chromatin accessibility in iPSCs and iPSC-derived neurons using BIRD (Big data Regression for predicting DNase I hypersensitivity).
Project description:We aim to profile the dynamic changes of gene expression dynamics during cortical neuron differentiation from human iPSCs. We used RNA-seq to map open chromatins in iPSCs, neural stem cells (NSCs) at day 33 and day 41.
Project description:Intermediate progenitors of GABAergic neurons obtained from the mouse embryo neocortex at E18. Additional info: http://srv02.medic.kumamoto-u.ac.jp/dept/morneuro/en_r_micro.html
Project description:In the present work, we gain insight into the impact of oligodendrocyte secreted factors on hippocampal GABAergic neuron physiology, and performed patch-clamp recordings followed by single-cell RNA sequencing of neurons. Our results demonstrate that the GABAergic neuron excitability is influenced by glial cells and oligodendrocyte-secreted factors. Moreover, we show specific ion channels alterations and find a correlation with electrophysiological parameters suggesting possible mechanisms for the OCM-induced regulation of neuronal function.
Project description:Neuropathic pain causes severe suffering and most patients are resilient to current therapies. A core element of neuropathic pain is the loss of inhibitory tone in the spinal cord. Previous studies have shown that foetal GABAergic neuron precursors can provide relief from pain. However, the source of these precursor cells and their multipotent status make them unsuitable for therapeutic use. Here we extend these findings by showing, for the first time, that spinally transplanted, terminally differentiated hiPSC-derived GABAergic (iGABAergic) neurons provide significant, long-term and safe relief from neuropathic pain induced by peripheral nerve injury in mice. Furthermore, iGABAergic Neuron transplants survive long term in the injured spinal cord and show evidence of synaptic integration. Together, this provides the proof in principle for the first viable GABAergic transplants to treat human neuropathic pain patients.