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Journal Articles Nature Communications Year : 2022

Evolutionary origin of vertebrate OCT4/POU5 functions in supporting pluripotency

Woranop Sukparangsi
Elena Morganti
  • Function : Author
Molly Lowndes
Melanie Weisser
  • Function : Author
Fella Hammachi
  • Function : Author
Hanna Peradziryi
  • Function : Author
Fabian Roske
Jurriaan Hölzenspies
  • Function : Author
Alessandra Livigni
  • Function : Author
Benoit Gilbert Godard
  • Function : Author
Stephen Frankenberg
  • Function : Author
Joshua Brickman


Abstract The support of pluripotent cells over time is an essential feature of development. In eutherian embryos, pluripotency is maintained from naïve states in peri-implantation to primed pluripotency at gastrulation. To understand how these states emerged, we reconstruct the evolutionary trajectory of the Pou5 gene family, which contains the central pluripotency factor OCT4. By coupling evolutionary sequence analysis with functional studies in mouse embryonic stem cells, we find that the ability of POU5 proteins to support pluripotency originated in the gnathostome lineage, prior to the generation of two paralogues, Pou5f1 and Pou5f3 via gene duplication. In osteichthyans, retaining both genes, the paralogues differ in their support of naïve and primed pluripotency. The specialization of these duplicates enables the diversification of function in self-renewal and differentiation. By integrating sequence evolution, cell phenotypes, developmental contexts and structural modelling, we pinpoint OCT4 regions sufficient for naïve pluripotency and describe their adaptation over evolutionary time.

Dates and versions

hal-03834932 , version 1 (31-10-2022)



Woranop Sukparangsi, Elena Morganti, Molly Lowndes, Hélène Mayeur, Melanie Weisser, et al.. Evolutionary origin of vertebrate OCT4/POU5 functions in supporting pluripotency. Nature Communications, 2022, 13 (1), pp.5537. ⟨10.1038/s41467-022-32481-z⟩. ⟨hal-03834932⟩
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