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

生物 计算生物学 模式生物 原肠化 器官发生 胚胎 细胞生物学 基因组学 基因 胚胎发生 遗传学 基因组
作者
Mai-Linh Ton,Daniel Keitley,Bart Theeuwes,Carolina Guibentif,Jonas Ahnfelt-Rønne,Thomas K. Andreassen,Fernando J. Calero‐Nieto,Iván Imaz-Rosshandler,Blanca Pijuan-Sala,Jennifer Nichols,Èlia Benito‐Gutiérrez,John C. Marioni,Berthold Göttgens
出处
期刊:Nature Cell Biology [Nature Portfolio]
卷期号:25 (7): 1061-1072 被引量:31
标识
DOI:10.1038/s41556-023-01174-0
摘要

Traditionally, the mouse has been the favoured 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. Here 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 neighbourhood comparison pipeline, we compare the transcriptional landscape of rabbit and mouse at the scale of the entire organism. We characterize the gene regulatory programmes underlying trophoblast differentiation and identify signalling interactions involving the yolk sac mesothelium during haematopoiesis. 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. Ton, Keitley et al. provide a morphological and molecular atlas of rabbit development. Comparative studies reveal that combining rabbit and mouse atlases can serve as a model for dissecting early primate development.
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