Evolutionary Origin of Vertebrate OCT4/POU5 Functions in Supporting Pluripotency

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 21

PMID 36130934

Authors

Woranop Sukparangsi

Elena Morganti

Molly Lowndes

Helene Mayeur

Melanie Weisser

Fella Hammachi

Hanna Peradziryi

Fabian Roske

Jurriaan Holzenspies

Alessandra Livigni

Benoit Gilbert Godard

Fumiaki Sugahara

Shigeru Kuratani

Guillermo Montoya

Stephen R Frankenberg

Sylvie Mazan

Joshua M Brickman

Affiliations

Soon will be listed here.

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.

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