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Defining murine organogenesis at single-cell resolution reveals a role for the leukotriene pathway in regulating blood progenitor formation.
Nature Cell Biology ( IF 21.3 ) Pub Date : 2018-01-08 , DOI: 10.1038/s41556-017-0013-z
Ximena Ibarra-Soria 1 , Wajid Jawaid 2, 3, 4 , Blanca Pijuan-Sala 2, 3 , Vasileios Ladopoulos 2, 3 , Antonio Scialdone 5, 6, 7 , David J Jörg 8, 9 , Richard C V Tyser 10 , Fernando J Calero-Nieto 2, 3 , Carla Mulas 3 , Jennifer Nichols 3 , Ludovic Vallier 6, 11, 12 , Shankar Srinivas 10 , Benjamin D Simons 3, 8, 9 , Berthold Göttgens 2, 3 , John C Marioni 1, 5, 6
Affiliation  

During gastrulation, cell types from all three germ layers are specified and the basic body plan is established 1 . However, molecular analysis of this key developmental stage has been hampered by limited cell numbers and a paucity of markers. Single-cell RNA sequencing circumvents these problems, but has so far been limited to specific organ systems 2 . Here, we report single-cell transcriptomic characterization of >20,000 cells immediately following gastrulation at E8.25 of mouse development. We identify 20 major cell types, which frequently contain substructure, including three distinct signatures in early foregut cells. Pseudo-space ordering of somitic progenitor cells identifies dynamic waves of transcription and candidate regulators, which are validated by molecular characterization of spatially resolved regions of the embryo. Within the endothelial population, cells that transition from haemogenic endothelial to erythro-myeloid progenitors specifically express Alox5 and its co-factor Alox5ap, which control leukotriene production. Functional assays using mouse embryonic stem cells demonstrate that leukotrienes promote haematopoietic progenitor cell generation. Thus, this comprehensive single-cell map can be exploited to reveal previously unrecognized pathways that contribute to tissue development.

中文翻译:

在单细胞分辨率下定义小鼠器官发生揭示了白三烯通路在调节血液祖细胞形成中的作用。

在原肠胚形成过程中,所有三个胚层的细胞类型都被指定,并建立了基本的身体计划 1 。然而,这一关键发育阶段的分子分析受到细胞数量有限和标记物缺乏的阻碍。单细胞 RNA 测序规避了这些问题,但迄今为止仅限于特定器官系统 2。在这里,我们报告了在小鼠发育的 E8.25 原肠胚形成后立即对 >20,000 个细胞进行的单细胞转录组学表征。我们确定了 20 种主要细胞类型,它们通常包含子结构,包括早期前肠细胞中的三个不同特征。体细胞祖细胞的伪空间排序识别转录的动态波和候选调节因子,这些通过胚胎空间分辨区域的分子表征得到验证。在内皮细胞群中,从造血内皮细胞转变为红髓祖细胞的细胞特异性表达 Alox5 及其辅助因子 Alox5ap,后者控制白三烯的产生。使用小鼠胚胎干细胞进行的功能测定表明,白三烯促进造血祖细胞的生成。因此,可以利用这种全面的单细胞图谱来揭示以前未被识别的促进组织发育的途径。
更新日期:2018-01-08
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