Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin.
Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin.
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DOI：
10.1038/s41593-023-01312-9
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发表时间：
2023-05
影响因子：
25
通讯作者：
Sundstrom, Erik
中科院分区：
文献类型：
--
作者：
Li, Xiaofei;Andrusivova, Zaneta;Czarnewski, Paulo;Langseth, Christoffer Mattsson;Andersson, Alma;Liu, Yang;Gyllborg, Daniel;Braun, Emelie;Larsson, Ludvig;Hu, Lijuan;Alekseenko, Zhanna;Lee, Hower;Avenel, Christophe;Kallner, Helena Kopp;Akesson, Elisabet;Adameyko, Igor;Nilsson, Mats;Linnarsson, Sten;Lundeberg, Joakim;Sundstrom, Erik
在人类发育中的脊髓细胞命运规范的时空调控仍然在很大程度上未知。在这项研究中，通过对单细胞和空间多组学数据进行综合分析，我们使用了16个产前人类样本，在受孕后5-12周内创建了一个全面的脊髓发育细胞图谱。这揭示了神经前体细胞的细胞命运承诺及其空间定位如何受特定基因集的时空调控。我们确定了人类脊髓发育相对于啮齿动物的独特事件，包括活性神经干细胞的早期静止，细胞分化的差异调节和细胞命运选择的独特时空遗传调节。此外，通过将我们的图谱与儿科室管膜瘤数据相结合，我们确定了癌症干细胞在进展过程中的特定分子特征和谱系特异性基因。因此，我们描绘了人类脊髓发育的时空遗传调控，并利用这些数据来获得疾病的洞察力。作者为人类脊髓的时空基因表达创建了一个全面的发育细胞图谱，揭示了发育过程中的物种特异性调控，并使用该图谱推断儿科室管膜瘤的新标记物。
The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of single-cell and spatial multi-omics data, we used 16 prenatal human samples to create a comprehensive developmental cell atlas of the spinal cord during post-conceptional weeks 5–12. This revealed how the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. We identified unique events in human spinal cord development relative to rodents, including earlier quiescence of active neural stem cells, differential regulation of cell differentiation and distinct spatiotemporal genetic regulation of cell fate choices. In addition, by integrating our atlas with pediatric ependymomas data, we identified specific molecular signatures and lineage-specific genes of cancer stem cells during progression. Thus, we delineate spatiotemporal genetic regulation of human spinal cord development and leverage these data to gain disease insight. The authors created a comprehensive developmental cell atlas for spatiotemporal gene expression of the human spinal cord, revealed species-specific regulation during development and used the atlas to infer novel markers for pediatric ependymomas.
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DOI：
10.1084/jem.20210040
发表时间：
2021-08-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Milich LM;Choi JS;Ryan C;Cerqueira SR;Benavides S;Yahn SL;Tsoulfas P;Lee JK
通讯作者：
Lee JK
影响因子：
4.6
作者：
Chalfoun J;Majurski M;Blattner T;Bhadriraju K;Keyrouz W;Bajcsy P;Brady M
通讯作者：
Brady M
影响因子：
5.9
作者：
Andersson A;Bergenstråhle J;Asp M;Bergenstråhle L;Jurek A;Fernández Navarro J;Lundeberg J
通讯作者：
Lundeberg J
影响因子：
16.6
作者：
Marqués-Torrejón MÁ;Williams CAC;Southgate B;Alfazema N;Clements MP;Garcia-Diaz C;Blin C;Arranz-Emparan N;Fraser J;Gammoh N;Parrinello S;Pollard SM
通讯作者：
Pollard SM
影响因子：
4.6
作者：
Delile, Julien;Rayon, Teresa;Sagner, Andreas
通讯作者：
Sagner, Andreas