Ayooshi Mitra, Amity University, Kolkata
Interspecies chimeras provide a unique platform for discovery and clinical use by probing early embryogenesis and regeneration. Interspecies chimeras are useful through interspecies blastocyst complementation to study human development and disease and also to produce functional human tissues. Cell competition involves a preserved fitness-sensing process during which adjoining less-fit but viable cells are eliminated by healthier cells. As a surveillance mechanism to ensure normal development and tissue homeostasis, cell competition has been proposed and has also been suggested to act as a barrier to chimerism among species.
Up until now, due to the lack of an in vitro model, cell competition has not been studied in an inter-species context during early development. In a recent study conducted by Zheng C et al., the researchers developed a co-culture strategy for interspecies pluripotent stem cells (PSC) and uncovered a previously unknown mode of cell competition among species. In primed but not naïve pluripotency interspecies PSC competition occurred among evolutionarily distant species. Through comparative transcriptome analysis, the researchers found that genes related to the signaling pathway of NF-2B showed up-regulation in loser human cells, among other things. The study showed that in human cells, genetic inactivation of a core component (P65) and an upstream regulator (MYD88) of the NF-βB complex can overcome human-mouse PSC competition, thus improving human cell survival and early mouse embryo chimerism.
This study discovers a new approach to cell competition and paves the way for the study of evolutionarily preserved mechanisms during early mammalian development that underlie competitive cell interaction. The suppression of PSC competition between species may facilitate the generation of human tissue in animals.
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Source: Zheng, C., Hu, Y., Sakurai, M. et al. Cell Competition Constitutes a Barrier for InterspeciesChimerism. Nature (2021). https://doi.org/10.1038/s41586-021-03273-0
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