Our translational research focuses on the development of iPS cell-based in vitro neurological disease models. We have reprogrammed iPS cells from patients with amyotrophic lateral sclerosis/frontotemporal dementia spectrum (ALS/FTD: SOD1 and C9orf72 mutations), spinocerebellar ataxia 14 (SCA14: PKCgamma mutation), dystonia (ACTB and GNAL mutations), and an idiopathic familial dysautonomia/peripheral neuropathy syndrome (uncharacterized mutation). We have developed differentiation protocols for neuronal precursors (NPCs), several neuron types (motoneurons, glutamatergic cortical neurons, generic GABAergic neurons) and astrocytes. We have also established a differentiation protocol for microglia developed by the group of Tormod Fladby, and we are working on a differentiation protocol for skeletal muscle and cardiomyocytes. We use these cell types to create 2D and 3D multiple cell type, compartmentalized microfluidic platforms, wherein the principal cell types involved in a disease are positioned in adjacent compartments permitting intercellular communication that simulates the anatomical and physiological situation in vivo. We are also developing a cerebellar organoid platform as a model for SCA14.
This translational research builds on decades of basic research into the structure, function and development of brainstem and spinal cord sensorimotor circuits in animal models, spanning from molecular programs of differentiation to patterns of synaptic connectivity to motor behavior, and on the mechanisms underlying adaptive plasticity following spinal cord injury.
Relevant publications from translational studies:
Sigurjonsson OE, Perreault MC, Egeland T, Glover JC. (2005) Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord. PNAS 102:5227-5232.
Boulland JL, Halasi G, Kasumacic N, Glover JC (2010) Xenotransplantation of human stem cells into the chicken embryo. J Vis Exp. 2010 Jul 11;(41). pii: 2071. doi: 10.3791/2071.
Boulland JL, Leung DS, Thuen M, Vik-Mo E, Joel M, Perreault MC, Langmoen IA, Haraldseth O, Glover JC (2012) Evaluation of intracellular labeling with micron-sized particles of iron oxide (MPIOs) as a general tool for in vitro and in vivo tracking of human stem and progenitor cells. Cell Transplant. 21(8):1743-1759.
Boulland JL, Mastrangelopoulou M, Boquest AC, Jakobsen R, Noer A, Glover JC, Collas P (2012) Epigenetic Regulation of Nestin Expression During Neurogenic Differentiation of Adipose Tissue Stem Cells. Stem Cells Dev. 22(7):1042-1052.
Boulland JL, Lambert FM, Züchner M, Ström S, Glover JC (2013) A neonatal mouse spinal cord injury model for assessing post-injury adaptive plasticity and human stem cell integration. PLoS One. 8(8):e71701.
Skogseid IM, Røsby O, Konglund A, Connelly JP, Nedregaard B, Jablonski GE, Kvernmo N, Stray-Pedersen A, Glover JC (2018) Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation. J Neurodev Disord. 10(1):17.
Liang KX, Vatne GH, Kristiansen CK, Ievglevskyi O, Kondratskaya E, Glover JC, Chen A, Sullivan GJ, Bindoff LA (2021) N-acetylcysteine amide ameliorates mitochondrial dysfunction and reduces oxidative stress in hiPSC-derived dopaminergic neurons with POLG mutation. Exp Neurol. 337:113536.
Akkouh IA, Hughes T, Steen VM, Glover JC, Andreassen OA, Djurovic S, Szabo A. (2021) Transcriptome analysis reveals disparate expression of inflammation-related miRNAs and their gene targets in iPSC-astrocytes from people with schizophrenia. Brain Behav Immun. 94:235-244.
Szabo A, Akkouh IA, Vandenberghe M, Osete JR, Hughes T, Heine V, Smeland OB, Glover JC, Andreassen OA, Djurovic S (2021) A human iPSC-astroglia neurodevelopmental model reveals divergent transcriptomic patterns in schizophrenia. Transl Psychiatry. 11(1):554.