A systematic review and embryological perspective of pluripotent stem cell-derived autonomic postganglionic neuron differentiation for human disease modeling
Human autonomic neuronal cell models are emerging as tools for modeling diseases such as cardiac arrhythmias. In this systematic review, we compared 33 articles applying 14 different protocols to generate sympathetic neurons and 3 different procedures to produce parasympathetic neurons. All methods...
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eLife Sciences Publications Ltd
2025-03-01
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| Online Access: | https://elifesciences.org/articles/103728 |
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| author | Thomas A Bos Elizaveta Polyakova Janine Maria van Gils Antoine AF de Vries Marie-José Goumans Christian Freund Marco C DeRuiter Monique RM Jongbloed |
| author_facet | Thomas A Bos Elizaveta Polyakova Janine Maria van Gils Antoine AF de Vries Marie-José Goumans Christian Freund Marco C DeRuiter Monique RM Jongbloed |
| author_sort | Thomas A Bos |
| collection | DOAJ |
| description | Human autonomic neuronal cell models are emerging as tools for modeling diseases such as cardiac arrhythmias. In this systematic review, we compared 33 articles applying 14 different protocols to generate sympathetic neurons and 3 different procedures to produce parasympathetic neurons. All methods involved the differentiation of human pluripotent stem cells, and none employed permanent or reversible cell immortalization. Almost all protocols were reproduced in multiple pluripotent stem cell lines, and over half showed evidence of neural firing capacity. Common limitations in the field are a lack of three-dimensional models and models that include multiple cell types. Sympathetic neuron differentiation protocols largely mirrored embryonic development, with the notable absence of migration, axon extension, and target-specificity cues. Parasympathetic neuron differentiation protocols may be improved by including several embryonic cues promoting cell survival, cell maturation, or ion channel expression. Moreover, additional markers to define parasympathetic neurons in vitro may support the validity of these protocols. Nonetheless, four sympathetic neuron differentiation protocols and one parasympathetic neuron differentiation protocol reported more than two-thirds of cells expressing autonomic neuron markers. Altogether, these protocols promise to open new research avenues of human autonomic neuron development and disease modeling. |
| format | Article |
| id | doaj-art-f5ea30b6a950455f82ff19b416bfbb98 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-f5ea30b6a950455f82ff19b416bfbb982025-08-20T01:54:54ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011410.7554/eLife.103728A systematic review and embryological perspective of pluripotent stem cell-derived autonomic postganglionic neuron differentiation for human disease modelingThomas A Bos0https://orcid.org/0000-0003-2837-7355Elizaveta Polyakova1https://orcid.org/0000-0002-9615-2871Janine Maria van Gils2Antoine AF de Vries3Marie-José Goumans4Christian Freund5Marco C DeRuiter6Monique RM Jongbloed7https://orcid.org/0000-0002-9132-0418Department of Anatomy and Embryology, Leiden University Medical Centre, Leiden, NetherlandsDepartment of Anatomy and Embryology, Leiden University Medical Centre, Leiden, NetherlandsDepartment of Anatomy and Embryology, Leiden University Medical Centre, Leiden, NetherlandsDepartment of Cardiology, Leiden University Medical Centre, Leiden, NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, NetherlandsDepartment of Anatomy and Embryology, Leiden University Medical Centre, Leiden, Netherlands; Leiden hiPSC Centre, Leiden University Medical Centre, Leiden, NetherlandsDepartment of Anatomy and Embryology, Leiden University Medical Centre, Leiden, Netherlands; Centre for Congenital Heart Disease Amsterdam-Leiden (CAHAL), Leiden, NetherlandsDepartment of Anatomy and Embryology, Leiden University Medical Centre, Leiden, Netherlands; Department of Cardiology, Leiden University Medical Centre, Leiden, Netherlands; Centre for Congenital Heart Disease Amsterdam-Leiden (CAHAL), Leiden, NetherlandsHuman autonomic neuronal cell models are emerging as tools for modeling diseases such as cardiac arrhythmias. In this systematic review, we compared 33 articles applying 14 different protocols to generate sympathetic neurons and 3 different procedures to produce parasympathetic neurons. All methods involved the differentiation of human pluripotent stem cells, and none employed permanent or reversible cell immortalization. Almost all protocols were reproduced in multiple pluripotent stem cell lines, and over half showed evidence of neural firing capacity. Common limitations in the field are a lack of three-dimensional models and models that include multiple cell types. Sympathetic neuron differentiation protocols largely mirrored embryonic development, with the notable absence of migration, axon extension, and target-specificity cues. Parasympathetic neuron differentiation protocols may be improved by including several embryonic cues promoting cell survival, cell maturation, or ion channel expression. Moreover, additional markers to define parasympathetic neurons in vitro may support the validity of these protocols. Nonetheless, four sympathetic neuron differentiation protocols and one parasympathetic neuron differentiation protocol reported more than two-thirds of cells expressing autonomic neuron markers. Altogether, these protocols promise to open new research avenues of human autonomic neuron development and disease modeling.https://elifesciences.org/articles/103728sympathetic neuronsparasympathetic neuronspluripotent stem cellsembryologyhumansystematic review |
| spellingShingle | Thomas A Bos Elizaveta Polyakova Janine Maria van Gils Antoine AF de Vries Marie-José Goumans Christian Freund Marco C DeRuiter Monique RM Jongbloed A systematic review and embryological perspective of pluripotent stem cell-derived autonomic postganglionic neuron differentiation for human disease modeling eLife sympathetic neurons parasympathetic neurons pluripotent stem cells embryology human systematic review |
| title | A systematic review and embryological perspective of pluripotent stem cell-derived autonomic postganglionic neuron differentiation for human disease modeling |
| title_full | A systematic review and embryological perspective of pluripotent stem cell-derived autonomic postganglionic neuron differentiation for human disease modeling |
| title_fullStr | A systematic review and embryological perspective of pluripotent stem cell-derived autonomic postganglionic neuron differentiation for human disease modeling |
| title_full_unstemmed | A systematic review and embryological perspective of pluripotent stem cell-derived autonomic postganglionic neuron differentiation for human disease modeling |
| title_short | A systematic review and embryological perspective of pluripotent stem cell-derived autonomic postganglionic neuron differentiation for human disease modeling |
| title_sort | systematic review and embryological perspective of pluripotent stem cell derived autonomic postganglionic neuron differentiation for human disease modeling |
| topic | sympathetic neurons parasympathetic neurons pluripotent stem cells embryology human systematic review |
| url | https://elifesciences.org/articles/103728 |
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