title: Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells.
abstract: Disturbances in neuronal differentiation and function are an underlying factor of many brain disorders. Zinc homeostasis and signaling are important mediators for a normal brain development and function, given that zinc deficiency was shown to result in cognitive and emotional deficits in animal models that might be associated with neurodevelopmental disorders. One underlying mechanism of the observed detrimental effects of zinc deficiency on the brain might be impaired proliferation and differentiation of stem cells participating in neurogenesis. Thus, to examine the molecular mechanisms regulating zinc metabolism and signaling in differentiating neurons, using a protocol for motor neuron differentiation, we characterized the expression of zinc homeostasis genes during neurogenesis using human induced pluripotent stem cells (hiPSCs) and evaluated the influence of altered zinc levels on the expression of zinc homeostasis genes, cell survival, cell fate, and neuronal function. Our results show that zinc transporters are highly regulated genes during neuronal differentiation and that low zinc levels are associated with decreased cell survival, altered neuronal differentiation, and, in particular, synaptic function. We conclude that zinc deficiency in a critical time window during brain development might influence brain function by modulating neuronal differentiation.
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Pfaender
authors.affiliation: Department of Anaesthesiology, University of Ulm, 89081 Ulm, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Föhr
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Lutz
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Putz
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany; Institute of Neuroanatomy, Eberhard Karls University of Tübingen, 72074 Tübingen, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Achberger
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany; Institute of Neuroanatomy, Eberhard Karls University of Tübingen, 72074 Tübingen, Germany.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Linta
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany; Institute of Neuroanatomy, Eberhard Karls University of Tübingen, 72074 Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebau
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany; WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, 89081 Ulm, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Grabrucker
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015032:Zinc / Q000378:metabolism*
chemical_list: D015032:Zinc