Generation of Retinal Ganglion Cells With Functional Axons From Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells. 2016

Taku Tanaka, and Tadashi Yokoi, and Fuminobu Tamalu, and Shu-Ichi Watanabe, and Sachiko Nishina, and Noriyuki Azuma
Department of Ophthalmology and Laboratory for Visual Science National Center for Child Health and Development, Tokyo, Japan.

OBJECTIVE We previously generated self-induced retinal ganglion cells (RGCs) with functional axons from human induced pluripotent stem cells (hiPSCs). We investigated whether self-induced RGCs from mouse embryonic stem cells (mESCs) and induced pluripotent stem cells (miPSCs) are realized by the similar induction protocol. METHODS Retinal ganglion cells were induced using a protocol in which floating embryoid bodies (EBs) were differentiated into a retinal cell lineage in three-dimensional culture and subsequently attached to two-dimensional culture dishes with brain-derived neurotrophic factor (BDNF) supplementation. RESULTS Retinal ganglion cells developed in an attached clump of cells originating from the optic vesicle, and most axons grew from RGC cell bodies at the margins of the clump. The differentiation of RGCs was confirmed by the expression of specific markers, including Brn3a and Math5. The axons contained neurofilament subtypes and tau, and manifested axonal transport and sodium-dependent action potentials. The RGCs derived from mESCs and miPSCs generally showed similar profiles, including RNA and protein expression levels and function. CONCLUSIONS Retinal ganglion cells generated from mESCs and miPSCs, especially the latter, may contribute to research associated with RGCs and to in vitro analyses of genetically modified mice.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000066450 Mouse Embryonic Stem Cells PLURIPOTENT STEM CELLS derived from the BLASTOCYST INNER CELL MASS of day 3.5 mouse embryos. mESC,Cells, Mouse Embryonic Stem,Mouse Embryonic Stem Cell,Stem Cells, Mouse Embryonic,mESCs
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001369 Axons Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. Axon
D001370 Axonal Transport The directed transport of ORGANELLES and molecules along nerve cell AXONS. Transport can be anterograde (from the cell body) or retrograde (toward the cell body). (Alberts et al., Molecular Biology of the Cell, 3d ed, pG3) Axoplasmic Flow,Axoplasmic Transport,Axoplasmic Streaming,Axonal Transports,Axoplasmic Flows,Axoplasmic Transports,Streaming, Axoplasmic,Transport, Axonal,Transport, Axoplasmic,Transports, Axonal,Transports, Axoplasmic
D012165 Retinal Ganglion Cells Neurons of the innermost layer of the retina, the internal plexiform layer. They are of variable sizes and shapes, and their axons project via the OPTIC NERVE to the brain. A small subset of these cells act as photoreceptors with projections to the SUPRACHIASMATIC NUCLEUS, the center for regulating CIRCADIAN RHYTHM. Cell, Retinal Ganglion,Cells, Retinal Ganglion,Ganglion Cell, Retinal,Ganglion Cells, Retinal,Retinal Ganglion Cell
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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