TY - JOUR
T1 - An atlas of rabbit development as a model for single-cell comparative genomics
AU - Nu Ton, Mai-Linh
AU - Keitley, Daniel
AU - Theeuwes, Bart
AU - Guibentif, Carolina
AU - Ahnfelt-Rønne, Jonas
AU - Kjærgaard Andreassen, Thomas
AU - Calero-Nieto, Fernando J.
AU - Imaz-Rosshandler, Ivan
AU - Pijuan-Sala, Blanca
AU - Nichols, Jennifer
AU - Benito-Gutiérrez, Èlia
AU - Marioni, John C
AU - Gottgens, Berthold
N1 - Funding Information:
We thank K. Katarzyna and the CRUK CI Genomics Core for their help with the 10x Genomics sample processing; R. Argelaguet for bioinformatic support; N. Wilson for assistance with the facilities and technical support; M. Rostovskaya for discussions around eutherian amnion; M. Keller (Gehlenborg lab) for help in setting up the Vitessce visualization platform. We also thank H. D. Farizi and S. D. Høiberg (Novo Nordisk) for help with rabbit embryo sectioning. M.-L.N.T. is funded by a Herchel Smith PhD Fellowship in Science. D.K. is funded by the Wellcome Mathematical Genomics and Medicine Programme at the University of Cambridge (PFZH/158 RG92770). C.G. was funded by the Swedish Research Council (2017-06278) and by a Swedish Childhood Cancer Fund position grant (TJ2021-0009). I.I.-R. was funded by the Wellcome Mathematical Genomics and Medicine Programme at the University of Cambridge (203942/Z/16/Z; RDAG/426RG86191). Work in the Gottgens group is supported by Wellcome, Bloodwise, MRC and CRUK, and by core support grants from Wellcome to the Wellcome-MRC Cambridge Stem Cell Institute. Work in the Marioni group is supported by core funding from CRUK (C9545/A29580) and by the European Molecular Biology Laboratory. Work in the È.B.-G. lab is supported by CRUK (C9545/A29580). This work was funded as part of a Wellcome grant (220379/B/20/Z) awarded to B.G., J.N. and J.C.M. and the WSSS Dev Ext Wellcome Grant (220152_C_20_Z) awarded to B.G. and J.C.M.
Funding Information:
Provision of time-mated rabbit embryos by Labcorp Early Development Laboratories Limited as well as scRNA-seq costs were supported by a research contract agreement with J.A.-R. and T.K.A. at Novo Nordisk A/S. È.B.-G. and J.C.M. have been employees of Genentech since September 2022.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/6/15
Y1 - 2023/6/15
N2 - 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.
AB - 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.
U2 - 10.1038/s41556-023-01174-0
DO - 10.1038/s41556-023-01174-0
M3 - Article
SN - 1465-7392
JO - Nature Cell Biology
JF - Nature Cell Biology
ER -