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Wellcome-MRC Cambridge Stem Cell Institute


A cross-species analysis of energy metabolism in mammalian embryogenesis

Cells of the early mammalian embryo face a unique challenge: to produce large numbers of progeny quickly while regulating appropriate cell differentiation in a short amount of time. The regulation of energy metabolism is crucial for these processes, both to supply energy for proliferation and to generate building blocks for embryonic development. Research published on Friday 17 June in the journal Nature Communications examines the role of metabolic flux in development, showing surprising similarities across various mammal species. 

The team of scientists led by Dr Thorsten Boroviak of the University of Cambridge Department of Physiology, Development and Neuroscience and the Wellcome-MRC Cambridge Stem Cell Institute used single-cell RNA sequencing to produce a dataset of early embryogenesis across six different species: human, cynomolgus monkey, marmoset, mouse, pig, and opossum. These species are separated by up to 160 million years of evolution between them, and therefore each has a unique developmental process, varying in the length of embryogenesis pre-implantation, the type of extraembryonic tissues, and implantation timings and methods.

“Previous studies in the mouse suggested that there is a metabolic shift upon embryo implantation. However, our study showed that metabolic gene regulation is independent of embryo implantation – probably across all mammals.” said Dr Thorsten Boroviak.

During embryonic development, the main two energy metabolism processes are glycolysis and oxidative phosphorylation (OxPhos). At different stages of development, these processes take turns influencing the embryo formation – for example, there is a rise in OxPhos as the blastocyst develops, then glycolysis increases in the following stage. The scientists conducting this research discovered that, despite the different methods and timings of formation, the metabolic conditions remained the same across the six different species. This indicates that mammalian embryogenesis is intrinsically regulated and independent of the timing and mode of implantation. 

Additionally, the team were also able to investigate the energy metabolism trends of in vitro models of embryonic development, confirming well-established metabolic characteristics of embryonic and epiblast-like stem cells.

In the future, the researchers hope that the datasets compiled throughout this study and the findings on the dynamics of energy metabolism in early mammalian embryos can be used as a resource for upcoming developmental research.



Malkowska, A., Penfold, C., Bergmann, S. et al. A hexa-species transcriptome atlas of mammalian embryogenesis delineates metabolic regulation across three different implantation modes. Nat Commun 13, 3407 (2022).

DOI: 10.1038/s41467-022-30194-x


This research is generously supported by the Wellcome Trust (WT RG89228) and the Centre for Trophoblast Research. A.M. is funded by the Wellcome Trust Developmental Mechanisms PhD programme. T.E.B is a Wellcome Trust - Royal Society Sir Henry Dale Fellow.