The single cell transcriptional landscape of mammalian organogenesis

The single cell transcriptional landscape of mammalian organogenesis

2019 February | Junyue Cao, Malte Spielmann, Xiaojie Qiu, Xingfan Huang, Daniel M. Ibrahim, Andrew J. Hill, Fan Zhang, Stefan Mundlos, Lena Christiansen, Frank J. Steemers, Cole Trapnell, and Jay Shendure
A single-cell transcriptional landscape of mammalian organogenesis was analyzed using sci-RNA-seq3, profiling ~2 million cells from 61 mouse embryos between E9.5 and E13.5. The resulting 'mouse organogenesis cell atlas' (MOCA) provides a comprehensive view of developmental processes during this critical window, identifying hundreds of cell types and 56 trajectories. The study reveals thousands of marker genes and explores gene expression dynamics within cell types and trajectories over time, including focused analyses of the apical ectodermal ridge, limb mesenchyme, and skeletal muscle. The study identifies 38 major cell types and 655 subtypes, with a median of 47,073 cells per major type. The atlas includes 572 subtypes, many of which are novel, and provides insights into the development of major organ systems. The study also reconstructs developmental trajectories, identifying 56 subtrajectories spanning all major systems, including the CNS, PNS, respiratory, digestive, cardiovascular, immune, lymphatic, urinary, endocrine, integumentary, skeletal, muscular, and reproductive systems. The study also investigates skeletal myogenesis, revealing a myogenic trajectory with multiple entry points and identifying key genes involved in myogenesis. The study highlights the importance of single-cell atlases in understanding developmental processes and identifying cell types and subtypes. The study also discusses the limitations of the current approach, including the sparse cell-by-gene matrix and the potential for missing extremely rare cell types. The study emphasizes the importance of community input and domain expertise in annotating and interpreting the data. The study also highlights the potential of single-cell atlases in understanding pleiotropic developmental disorders and the role of genes and regulatory sequences in development. The study concludes that the data constitute a potentially foundational resource for the mammalian developmental biology field.A single-cell transcriptional landscape of mammalian organogenesis was analyzed using sci-RNA-seq3, profiling ~2 million cells from 61 mouse embryos between E9.5 and E13.5. The resulting 'mouse organogenesis cell atlas' (MOCA) provides a comprehensive view of developmental processes during this critical window, identifying hundreds of cell types and 56 trajectories. The study reveals thousands of marker genes and explores gene expression dynamics within cell types and trajectories over time, including focused analyses of the apical ectodermal ridge, limb mesenchyme, and skeletal muscle. The study identifies 38 major cell types and 655 subtypes, with a median of 47,073 cells per major type. The atlas includes 572 subtypes, many of which are novel, and provides insights into the development of major organ systems. The study also reconstructs developmental trajectories, identifying 56 subtrajectories spanning all major systems, including the CNS, PNS, respiratory, digestive, cardiovascular, immune, lymphatic, urinary, endocrine, integumentary, skeletal, muscular, and reproductive systems. The study also investigates skeletal myogenesis, revealing a myogenic trajectory with multiple entry points and identifying key genes involved in myogenesis. The study highlights the importance of single-cell atlases in understanding developmental processes and identifying cell types and subtypes. The study also discusses the limitations of the current approach, including the sparse cell-by-gene matrix and the potential for missing extremely rare cell types. The study emphasizes the importance of community input and domain expertise in annotating and interpreting the data. The study also highlights the potential of single-cell atlases in understanding pleiotropic developmental disorders and the role of genes and regulatory sequences in development. The study concludes that the data constitute a potentially foundational resource for the mammalian developmental biology field.
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[slides and audio] The single cell transcriptional landscape of mammalian organogenesis