| 论文题目： | Identification of HSC/MPP expansion units in fetal liver by single-cell spatiotemporal transcriptomics |
| 论文题目英文： | |
| 作者： | Gao,Suwei;Shi,Qiang;Zhang,Yifan;Liang,Guixian;Kang,Zhixin;Huang,Baofeng;Ma,Dongyuan;Wang,Lu;Jiao,Jianwei;Fang,Xiangdong;Xu,Cheng-Ran;Liu,Longqi;Xu,Xun;Gottgens,Berthold;Li,Cheng;Liu,Feng |
| 论文出处： | |
| 年： | 2021 |
| 卷： | 32 |
| 期： | 1 |
| 页： | 38-53 |
| 联系作者： | 刘峰 |
| 发表期刊： | Cell Research |
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| 论文连接 | http://www-nature-com-s.webvpn.ioz.ac.cn/articles/s41422-021-00540-7 |
| 影响因子： | 46.378 |
| 摘要: | Limited knowledge of cellular and molecular mechanisms underlying hematopoietic stem cell and multipotent progenitor (HSC/MPP) expansion within their native niche has impeded the application of stem cell-based therapies for hematological malignancies. Here, we constructed a spatiotemporal transcriptome map of mouse fetal liver (FL) as a platform for hypothesis generation and subsequent experimental validation of novel regulatory mechanisms. Single-cell transcriptomics revealed three transcriptionally heterogeneous HSC/MPP subsets, among which a CD93-enriched subset exhibited enhanced stem cell properties. Moreover, by employing integrative analysis of single-cell and spatial transcriptomics, we identified novel HSC/MPP 'pocket-like' units (HSC PLUS), composed of niche cells (hepatoblasts, stromal cells, endothelial cells, and macrophages) and enriched with growth factors. Unexpectedly, macrophages showed an 11-fold enrichment in the HSC PLUS. Functionally, macrophage-HSC/MPP co-culture assay and candidate molecule testing, respectively, validated the supportive role of macrophages and growth factors (MDK, PTN, and IGFBP5) in HSC/MPP expansion. Finally, cross-species analysis and functional validation showed conserved cell-cell interactions and expansion mechanisms but divergent transcriptome signatures between mouse and human FL HSCs/MPPs. Taken together, these results provide an essential resource for understanding HSC/MPP development in FL, and novel insight into functional HSC/MPP expansion ex vivo. |
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