title: Differentiation of human pluripotent stem cells into Medial Ganglionic Eminence vs. Caudal Ganglionic Eminence cells.
abstract: Human pluripotent stem cells (PSCs) represent an opportunity to study human development in vitro, to model diseases in a dish, to screen drugs as well as to provide an unlimited and ethically unimpeded source of therapeutic cells. Cortical GABAergic interneurons, which are generated from Medial Ganglionic Eminence (MGE) cells and Caudal Ganglionic Eminence (CGE) cells during embryonic development, regulate cortical neural networks by providing inhibitory inputs. Their malfunction, resulting in failure to intricately regulate neural circuit balance, has been implicated in brain diseases, such as schizophrenia, autism and epilepsy. In this study, using combinatorial and temporal modulation of developmentally relevant dorsoventral and rostrocaudal signaling pathways, we efficiently generated MGE cells vs. CGE cells from human PSCs, which predominantly generate Parvalbumin-expressing or Somatostatin-expressing interneurons vs. Calretinin-expressing interneurons, respectively. Efficient generation of specific differentiated progenies of hPSCs as shown in this study will be a pivotal step to realize the full potential of hPSCs for regenerative medicine, developmental studies, disease modeling, bioassay, and drug screening.
authors.affiliation: Translational Stem Cell Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Tae-Gon
authors.initials: TG
authors.lastname: Kim
authors.affiliation: Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Translational Stem Cell Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA; Harvard Stem Cell Institute, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA. Electronic address: schung@mclean.harvard.edu.
authors.forename: Sangmi
authors.initials: S
authors.lastname: Chung
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D059330:GABAergic Neurons / Q000378:metabolism; D020869:Gene Expression Profiling; D000066449:Human Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D007395:Interneurons / Q000378:metabolism; D008856:Microscopy, Fluorescence; D039904:Pluripotent Stem Cells / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology
keywords: Caudal Ganglionic Eminence; Differentiation; Interneurons; Medial Ganglionic Eminence; Pluripotent stem cells