Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system
Abstract Background The detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molec...
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-024-03728-x |
| _version_ | 1827277269045870592 |
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| author | Yingqi Li Jinjin Duan You Li Meihui Zhang Jiaan Wu Guanhao Wang Shuanqing Li Zhangsen Hu Yi Qu Yunhe Li Xiran Hu Fei Guo Lining Cao Jianfeng Lu |
| author_facet | Yingqi Li Jinjin Duan You Li Meihui Zhang Jiaan Wu Guanhao Wang Shuanqing Li Zhangsen Hu Yi Qu Yunhe Li Xiran Hu Fei Guo Lining Cao Jianfeng Lu |
| author_sort | Yingqi Li |
| collection | DOAJ |
| description | Abstract Background The detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molecular events during human SN development process. Methods A fifth Ewing variant (FEV)-EGFP reporter system was established by CRISPR/Cas9 technology to indicate SN since postmitotic stage. FACS was performed to purify SN from the heterogeneous cell populations. RNA-sequencing analysis was performed for cells at four key stages of differentiation (pluripotent stem cells, serotonergic neural progenitors, purified postmitotic SN and purifed mature SN) to explore the transcriptomic dynamics during SN differentiation. Results We found that human serotonergic fate specification may commence as early as day 21 of differentiation from human pluripotent stem cells. Furthermore, the transcriptional factors ZIC1, HOXA2 and MSX2 were identified as the hub genes responsible for orchestrating serotonergic fate determination. Conclusions For the first time, we exposed the developmental transcriptomic profiles of human SN via FEV reporter system, which will further our understanding for the development process of human SN. Graphical Abstract |
| first_indexed | 2024-04-24T07:18:06Z |
| format | Article |
| id | doaj.art-06e6e4f9f65a44be8acc6c99549514a4 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-24T07:18:06Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-06e6e4f9f65a44be8acc6c99549514a42024-04-21T11:10:48ZengBMCStem Cell Research & Therapy1757-65122024-04-0115111610.1186/s13287-024-03728-xTranscriptomic profiling across human serotonin neuron differentiation via the FEV reporter systemYingqi Li0Jinjin Duan1You Li2Meihui Zhang3Jiaan Wu4Guanhao Wang5Shuanqing Li6Zhangsen Hu7Yi Qu8Yunhe Li9Xiran Hu10Fei Guo11Lining Cao12Jianfeng Lu13Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityShanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityAbstract Background The detailed transcriptomic profiles during human serotonin neuron (SN) differentiation remain elusive. The establishment of a reporter system based on SN terminal selector holds promise to produce highly-purified cells with an early serotonergic fate and help elucidate the molecular events during human SN development process. Methods A fifth Ewing variant (FEV)-EGFP reporter system was established by CRISPR/Cas9 technology to indicate SN since postmitotic stage. FACS was performed to purify SN from the heterogeneous cell populations. RNA-sequencing analysis was performed for cells at four key stages of differentiation (pluripotent stem cells, serotonergic neural progenitors, purified postmitotic SN and purifed mature SN) to explore the transcriptomic dynamics during SN differentiation. Results We found that human serotonergic fate specification may commence as early as day 21 of differentiation from human pluripotent stem cells. Furthermore, the transcriptional factors ZIC1, HOXA2 and MSX2 were identified as the hub genes responsible for orchestrating serotonergic fate determination. Conclusions For the first time, we exposed the developmental transcriptomic profiles of human SN via FEV reporter system, which will further our understanding for the development process of human SN. Graphical Abstracthttps://doi.org/10.1186/s13287-024-03728-xSerotonin neuronsFEV-EGFP reporterHuman pluripotent stem cellsDifferentiationCRISPR/Cas9 |
| spellingShingle | Yingqi Li Jinjin Duan You Li Meihui Zhang Jiaan Wu Guanhao Wang Shuanqing Li Zhangsen Hu Yi Qu Yunhe Li Xiran Hu Fei Guo Lining Cao Jianfeng Lu Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system Stem Cell Research & Therapy Serotonin neurons FEV-EGFP reporter Human pluripotent stem cells Differentiation CRISPR/Cas9 |
| title | Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system |
| title_full | Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system |
| title_fullStr | Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system |
| title_full_unstemmed | Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system |
| title_short | Transcriptomic profiling across human serotonin neuron differentiation via the FEV reporter system |
| title_sort | transcriptomic profiling across human serotonin neuron differentiation via the fev reporter system |
| topic | Serotonin neurons FEV-EGFP reporter Human pluripotent stem cells Differentiation CRISPR/Cas9 |
| url | https://doi.org/10.1186/s13287-024-03728-x |
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