Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly
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- Human induced pluripotent stem cells (hiPSCs) have revolutionized the generation of experimental disease models, but the development of protocols for the differentiation of functionally active neuronal subtypes with defined specification is still in its infancy. While dysfunction of the brain serotonin (5-HT) system has been implicated in the etiology of various neuropsychiatric disorders, investigation of functional human 5-HT specific neurons in vitro has been restricted by technical limitations. We describe an efficient generation ofHuman induced pluripotent stem cells (hiPSCs) have revolutionized the generation of experimental disease models, but the development of protocols for the differentiation of functionally active neuronal subtypes with defined specification is still in its infancy. While dysfunction of the brain serotonin (5-HT) system has been implicated in the etiology of various neuropsychiatric disorders, investigation of functional human 5-HT specific neurons in vitro has been restricted by technical limitations. We describe an efficient generation of functionally active neurons from hiPSCs displaying 5-HT specification by modification of a previously reported protocol. Furthermore, 5-HT specific neurons were characterized using high-end fluorescence imaging including super-resolution microscopy in combination with electrophysiological techniques. Differentiated hiPSCs synthesize 5-HT, express specific markers, such as tryptophan hydroxylase 2 and 5-HT transporter, and exhibit an electrophysiological signature characteristic of serotonergic neurons, with spontaneous rhythmic activities, broad action potentials and large afterhyperpolarization potentials. 5-HT specific neurons form synapses reflected by the expression of pre- and postsynaptic proteins, such as Bassoon and Homer. The distribution pattern of Bassoon, a marker of the active zone along the soma and extensions of neurons, indicates functionality via volume transmission. Among the high percentage of 5-HT specific neurons (~ 42%), a subpopulation of CDH13 + cells presumably designates dorsal raphe neurons. hiPSC-derived 5-HT specific neuronal cell cultures reflect the heterogeneous nature of dorsal and median raphe nuclei and may facilitate examining the association of serotonergic neuron subpopulations with neuropsychiatric disorders.…
Autor(en): | Charline Jansch, Georg C. Ziegler, Andrea Forero, Sina Gredy, Sina Wäldchen, Maria Rosaria Vitale, Evgeniy Svirin, Johanna E. M. Zöller, Jonas Waider, Katharina Günther, Frank Edenhofer, Markus Sauer, Erhard Wischmeyer, Klaus-Peter Lesch |
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URN: | urn:nbn:de:bvb:20-opus-268519 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Physiologisches Institut |
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie | |
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Journal of Neural Transmission |
ISSN: | 1435-1463 |
Erscheinungsjahr: | 2021 |
Band / Jahrgang: | 128 |
Heft / Ausgabe: | 2 |
Seitenangabe: | 225-241 |
Originalveröffentlichung / Quelle: | Journal of Neural Transmission 2021, 128(2):225-241. DOI: 10.1007/s00702-021-02303-5 |
DOI: | https://doi.org/10.1007/s00702-021-02303-5 |
PubMed-ID: | https://pubmed.ncbi.nlm.nih.gov/33560471 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Cadherin-13 (CDH13); human induced pluripotent stem cell (hiPSC); median and dorsal raphe; neuropsychiatric disorders; serotonin-specific neurons; synapse formation |
Datum der Freischaltung: | 08.06.2022 |
EU-Projektnummer / Contract (GA) number: | 602805 |
EU-Projektnummer / Contract (GA) number: | 728018 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |