Uncovering the role of FOXA2 in the Development of Human Serotonin Neurons
文献类型：期刊论文
| 作者 | Xu, Ting1; Cao, Lining1; Duan, Jinjin1; Li, Yingqi1; Li, You1; Hu, Zhangsen1; Li, Shuanqing1; Zhang, Meihui1; Wang, Guanhao1; Guo, Fei2 |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2023-09-07 |
| 页码 | 15 |
| 关键词 | FOXA2 human pluripotent stem cells RA signaling serotonin neurons SHH signaling |
| DOI | 10.1002/advs.202303884 |
| 通讯作者 | Lu, Jianfeng(lu.jianfeng@tongji.edu.cn) |
| 英文摘要 | Directed differentiation of serotonin neurons (SNs) from human pluripotent stem cells (hPSCs) provides a valuable tool for uncovering the mechanism of human SN development and the associated neuropsychiatric disorders. Previous studies report that FOXA2 is expressed by serotonergic progenitors (SNPs) and functioned as a serotonergic fate determinant in mouse. However, in the routine differentiation experiments, it is accidentally found that less SNs and more non-neuronal cells are obtained from SNP stage with higher percentage of FOXA2-positive cells. This phenomenon prompted them to question the role of FOXA2 as an intrinsic fate determinant for human SN differentiation. Herein, by direct differentiation of engineered hPSCs into SNs, it is found that the SNs are not derived from FOXA2-lineage cells; FOXA2-knockout hPSCs can still differentiate into mature and functional SNs with typical serotonergic identity; FOXA2 overexpression suppresses the SN differentiation, indicating that FOXA2 is not intrinsically required for human SN differentiation. Furthermore, repressing FOXA2 expression by retinoic acid (RA) and dynamically modulating Sonic Hedgehog (SHH) signaling pathway promotes human SN differentiation. This study uncovers the role of FOXA2 in human SN development and improves the differentiation efficiency of hPSCs into SNs by repressing FOXA2 expression. By direct differentiation of engineered human pluripotent stem cells (hPSCs) into serotonin neurons (SNs), this study reveals that human SNs are not derived from FOXA2-lineage cells; FOXA2-knockout hPSCs can still differentiate into mature and functional SNs; FOXA2-overexpression suppresses SN differentiation. This study uncovers the role of FOXA2 in human SN development and improves the differentiation efficiency toward SNs by repressing FOXA2 expression.image |
| WOS关键词 | CELL FATE ; STEM-CELLS ; GENERATION ; SHH ; SPECIFICATION ; PROGENITORS ; SYSTEM ; NKX2.2 ; MOTOR ; BETA |
| 资助项目 | National Key Research and Development Program of China[2021YFA1101300] ; National Key Research and Development Program of China[2017YFA0104100] ; National Natural Science Foundation of China[31771644] ; National Natural Science Foundation of China[81801331] ; National Natural Science Foundation of China[31930068] ; Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center) Talent introduction plan[KYPT202204] ; Fundamental Research Funds for the Central Universities[22120230292] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:001059819400001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307067]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Lu, Jianfeng |
| 作者单位 | 1.Tongji Univ, Shanghai YangZhi Rehabil Hosp, Shanghai Sunshine Rehabil Ctr, Frontier Sci Ctr Stem Cell Res,Sch Life Sci & Tech, Shanghai 200092, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Tongji Univ, Suzhou Inst, Suzhou 215101, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Ting,Cao, Lining,Duan, Jinjin,et al. Uncovering the role of FOXA2 in the Development of Human Serotonin Neurons[J]. ADVANCED SCIENCE,2023:15. |
| APA | Xu, Ting.,Cao, Lining.,Duan, Jinjin.,Li, Yingqi.,Li, You.,...&Lu, Jianfeng.(2023).Uncovering the role of FOXA2 in the Development of Human Serotonin Neurons.ADVANCED SCIENCE,15. |
| MLA | Xu, Ting,et al."Uncovering the role of FOXA2 in the Development of Human Serotonin Neurons".ADVANCED SCIENCE (2023):15. |
入库方式： OAI收割
来源：上海药物研究所
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