Development of synthetic modulator enabling long-term propagation and neurogenesis of human embryonic stem cell-derived neural progenitor cells
Abstract Neural progenitor cells (NPCs) are essential for in vitro drug screening and cell-based therapies for brain-related disorders, necessitating well-defined and reproducible culture systems. Current strategies employing protein growth factors pose challenges in terms of both reproducibility an...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Biological Research |
| Online Access: | https://doi.org/10.1186/s40659-023-00471-0 |
| _version_ | 1797630423633756160 |
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| author | Ceheng Liao Ying Guan Jihui Zheng Xue Wang Meixia Wang Zhouhai Zhu Qiyuan Peng Hong-Hui Wang Meng Li |
| author_facet | Ceheng Liao Ying Guan Jihui Zheng Xue Wang Meixia Wang Zhouhai Zhu Qiyuan Peng Hong-Hui Wang Meng Li |
| author_sort | Ceheng Liao |
| collection | DOAJ |
| description | Abstract Neural progenitor cells (NPCs) are essential for in vitro drug screening and cell-based therapies for brain-related disorders, necessitating well-defined and reproducible culture systems. Current strategies employing protein growth factors pose challenges in terms of both reproducibility and cost. In this study, we developed a novel DNA-based modulator to regulate FGFR signaling in NPCs, thereby facilitating the long-term maintenance of stemness and promoting neurogenesis. This DNA-based FGFR-agonist effectively stimulated FGFR1 phosphorylation and activated the downstream ERK signaling pathway in human embryonic stem cell (HESC)-derived NPCs. We replaced the basic fibroblast growth factor (bFGF) in the culture medium with our DNA-based FGFR-agonist to artificially modulate FGFR signaling in NPCs. Utilizing a combination of cell experiments and bioinformatics analyses, we showed that our FGFR-agonist could enhance NPC proliferation, direct migration, and promote neurosphere formation, thus mimicking the functions of bFGF. Notably, transcriptomic analysis indicated that the FGFR-agonist could specifically influence the transcriptional program associated with stemness while maintaining the neuronal differentiation program, closely resembling the effects of bFGF. Furthermore, our culture conditions allowed for the successful propagation of NPCs through over 50 passages while retaining their ability to efficiently differentiate into neurons. Collectively, our approach offers a highly effective method for expanding NPCs, thereby providing new avenues for disease-in-dish research and drug screening aimed at combating neural degeneration. |
| first_indexed | 2024-03-11T11:07:08Z |
| format | Article |
| id | doaj.art-0d062d7d1e3646c9a124a384cbb04249 |
| institution | Directory Open Access Journal |
| issn | 0717-6287 |
| language | English |
| last_indexed | 2024-03-11T11:07:08Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj.art-0d062d7d1e3646c9a124a384cbb042492023-11-12T12:07:12ZengBMCBiological Research0717-62872023-11-0156111510.1186/s40659-023-00471-0Development of synthetic modulator enabling long-term propagation and neurogenesis of human embryonic stem cell-derived neural progenitor cellsCeheng Liao0Ying Guan1Jihui Zheng2Xue Wang3Meixia Wang4Zhouhai Zhu5Qiyuan Peng6Hong-Hui Wang7Meng Li8College of Biology, Hunan UniversityJoint Institute of Tobacco and HealthCollege of Biology, Hunan UniversityCollege of Biology, Hunan UniversityCollege of Biology, Hunan UniversityJoint Institute of Tobacco and HealthJoint Institute of Tobacco and HealthCollege of Biology, Hunan UniversityJoint Institute of Tobacco and HealthAbstract Neural progenitor cells (NPCs) are essential for in vitro drug screening and cell-based therapies for brain-related disorders, necessitating well-defined and reproducible culture systems. Current strategies employing protein growth factors pose challenges in terms of both reproducibility and cost. In this study, we developed a novel DNA-based modulator to regulate FGFR signaling in NPCs, thereby facilitating the long-term maintenance of stemness and promoting neurogenesis. This DNA-based FGFR-agonist effectively stimulated FGFR1 phosphorylation and activated the downstream ERK signaling pathway in human embryonic stem cell (HESC)-derived NPCs. We replaced the basic fibroblast growth factor (bFGF) in the culture medium with our DNA-based FGFR-agonist to artificially modulate FGFR signaling in NPCs. Utilizing a combination of cell experiments and bioinformatics analyses, we showed that our FGFR-agonist could enhance NPC proliferation, direct migration, and promote neurosphere formation, thus mimicking the functions of bFGF. Notably, transcriptomic analysis indicated that the FGFR-agonist could specifically influence the transcriptional program associated with stemness while maintaining the neuronal differentiation program, closely resembling the effects of bFGF. Furthermore, our culture conditions allowed for the successful propagation of NPCs through over 50 passages while retaining their ability to efficiently differentiate into neurons. Collectively, our approach offers a highly effective method for expanding NPCs, thereby providing new avenues for disease-in-dish research and drug screening aimed at combating neural degeneration.https://doi.org/10.1186/s40659-023-00471-0 |
| spellingShingle | Ceheng Liao Ying Guan Jihui Zheng Xue Wang Meixia Wang Zhouhai Zhu Qiyuan Peng Hong-Hui Wang Meng Li Development of synthetic modulator enabling long-term propagation and neurogenesis of human embryonic stem cell-derived neural progenitor cells Biological Research |
| title | Development of synthetic modulator enabling long-term propagation and neurogenesis of human embryonic stem cell-derived neural progenitor cells |
| title_full | Development of synthetic modulator enabling long-term propagation and neurogenesis of human embryonic stem cell-derived neural progenitor cells |
| title_fullStr | Development of synthetic modulator enabling long-term propagation and neurogenesis of human embryonic stem cell-derived neural progenitor cells |
| title_full_unstemmed | Development of synthetic modulator enabling long-term propagation and neurogenesis of human embryonic stem cell-derived neural progenitor cells |
| title_short | Development of synthetic modulator enabling long-term propagation and neurogenesis of human embryonic stem cell-derived neural progenitor cells |
| title_sort | development of synthetic modulator enabling long term propagation and neurogenesis of human embryonic stem cell derived neural progenitor cells |
| url | https://doi.org/10.1186/s40659-023-00471-0 |
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