Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells
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 mod...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2016/3760702 |
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| author | Stefanie Pfaender Karl Föhr Anne-Kathrin Lutz Stefan Putz Kevin Achberger Leonhard Linta Stefan Liebau Tobias M. Boeckers Andreas M. Grabrucker |
| author_facet | Stefanie Pfaender Karl Föhr Anne-Kathrin Lutz Stefan Putz Kevin Achberger Leonhard Linta Stefan Liebau Tobias M. Boeckers Andreas M. Grabrucker |
| author_sort | Stefanie Pfaender |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ae6fcb3ac2e34526aebd098301d867d4 |
| institution | OA Journals |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-ae6fcb3ac2e34526aebd098301d867d42025-08-20T02:23:34ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/37607023760702Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem CellsStefanie Pfaender0Karl Föhr1Anne-Kathrin Lutz2Stefan Putz3Kevin Achberger4Leonhard Linta5Stefan Liebau6Tobias M. Boeckers7Andreas M. Grabrucker8Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyDepartment of Anaesthesiology, University of Ulm, 89081 Ulm, GermanyInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyInstitute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, GermanyDisturbances 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.http://dx.doi.org/10.1155/2016/3760702 |
| spellingShingle | Stefanie Pfaender Karl Föhr Anne-Kathrin Lutz Stefan Putz Kevin Achberger Leonhard Linta Stefan Liebau Tobias M. Boeckers Andreas M. Grabrucker Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells Neural Plasticity |
| title | Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells |
| title_full | Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells |
| title_fullStr | Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells |
| title_full_unstemmed | Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells |
| title_short | Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells |
| title_sort | cellular zinc homeostasis contributes to neuronal differentiation in human induced pluripotent stem cells |
| url | http://dx.doi.org/10.1155/2016/3760702 |
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