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Defining murine organogenesis at single-cell resolution reveals a role for the leukotriene pathway in regulating blood progenitor formation.

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Ibarra-Soria, Ximena 
Jawaid, Wajid 
Pijuan-Sala, Blanca 
Ladopoulos, Vasileios 
Scialdone, Antonio 


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.



5-Lipoxygenase-Activating Proteins, Animals, Arachidonate 5-Lipoxygenase, Cell Lineage, Embryonic Development, Gastrulation, Hematopoietic Stem Cells, High-Throughput Nucleotide Sequencing, Leukotrienes, Mice, Mouse Embryonic Stem Cells, Organogenesis, Signal Transduction, Single-Cell Analysis

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Nat Cell Biol

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Springer Science and Business Media LLC
Leukaemia & Lymphoma Research (12029)
Wellcome Trust (105031/D/14/Z)
Cancer Research UK (21762)
National Institute of Diabetes and Digestive and Kidney Diseases (R24DK106766)
Wellcome Trust (098357/Z/12/Z)
Wellcome Trust (108438/E/15/Z)
Medical Research Council (MR/M008975/1)
Medical Research Council (G0900951)
Medical Research Council (MC_PC_12009)
Wellcome Trust (206328/Z/17/Z)
Medical Research Council (G0900951/1)