title: Humanized neuronal chimeric mouse brain generated by neonatally engrafted human iPSC-derived primitive neural progenitor cells.
abstract: The creation of a humanized chimeric mouse nervous system permits the study of human neural development and disease pathogenesis using human cells in vivo. Humanized glial chimeric mice with the brain and spinal cord being colonized by human glial cells have been successfully generated. However, generation of humanized chimeric mouse brains repopulated by human neurons to possess a high degree of chimerism have not been well studied. Here we created humanized neuronal chimeric mouse brains by neonatally engrafting the distinct and highly neurogenic human induced pluripotent stem cell (hiPSC)-derived rosette-type primitive neural progenitors. These neural progenitors predominantly differentiate to neurons, which disperse widely throughout the mouse brain with infiltration of the cerebral cortex and hippocampus at 6 and 13 months after transplantation. Building upon the hiPSC technology, we propose that this potentially unique humanized neuronal chimeric mouse model will provide profound opportunities to define the structure, function, and plasticity of neural networks containing human neurons derived from a broad variety of neurological disorders.
authors.affiliation: Department of Developmental Neuroscience, Munroe-Meyer Institute.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Developmental Neuroscience, Munroe-Meyer Institute.
authors.forename: Woo-Yang
authors.initials: WY
authors.lastname: Kim
authors.affiliation: Department of Developmental Neuroscience, Munroe-Meyer Institute.|Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002678:Chimera; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D033581:Stem Cell Transplantation