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An atlas of rabbit development as a model for single-cell comparative genomics

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Traditionally, the mouse has been the favored vertebrate model for biomedical research, due to its experimental and genetic tractability. However, non-rodent embryological studies highlight that many aspects of early mouse development, such as its egg-cylinder gastrulation and method of implantation, diverge from other mammals, thus complicating inferences about human development. Like the human embryo, rabbits develop as a flat-bilaminar disc. In this study, we constructed a morphological and molecular atlas of rabbit development. We report transcriptional and chromatin accessibility profiles for over 180,000 single cells and high-resolution histology sections from embryos spanning gastrulation, implantation, amniogenesis, and early organogenesis. Using a novel computational pipeline, we compare the transcriptional landscape of rabbit and mouse at the scale of the entire organism. We characterize the gene regulatory programs underlying trophoblast differentiation and identify signaling interactions involving the yolk sac mesothelium during hematopoiesis. We demonstrate how the combination of both rabbit and mouse atlases can be leveraged to extract new biological insights from sparse macaque and human data. The datasets and computational pipelines reported here set a framework for a broader cross-species approach to decipher early mammalian development, and are readily adaptable to deploy single cell comparative genomics more broadly across biomedical research.



Cambridge Stem Cell Institute

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Nature Cell Biology

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Nature Research
Wellcome Trust (220379/B/20/Z)
Wellcome Trust (220379/Z/20/Z)
Wellcome Trust (203151/A/16/Z)
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (108864/B/15/Z)
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