Abstract
BackgroundIn mouse ES cells, the function of Sox2 is essential for the maintenance of pluripotency. Since the Sox-family of transcription factors are well conserved in the animal kingdom, addressing the evolutionary origin of Sox2 function in pluripotent stem cells is intriguing from the perspective of understanding the origin of pluripotency.ResultsHere we approach this question using a functional complementation assay in inducible Sox2-null ES cells. Assaying mouse Sox proteins from different Groups, we found that only Group B1 and Group G proteins were able to support pluripotency. Interestingly, invertebrate homologs of mammalian Group B1 Sox proteins were able to replace the pluripotency-associated function of mouse Sox2. Moreover, the mouse ES cells rescued by the Drosophila SoxNeuro protein are able to contribute to chimeric embryos.ConclusionsThese data indicate that the function of mouse Sox2 supporting pluripotency is based on an evolutionally conserved activity of the Group B1 Sox family. Since pluripotent stem cell population in developmental process could be regarded as the evolutional novelty in vertebrates, it could be regarded as a co-optional use of their evolutionally conserved function.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0755-4) contains supplementary material, which is available to authorized users.
Highlights
In mouse embryonic stem (ES) cells, the function of Sox2 is essential for the maintenance of pluripotency
These data indicate that the function of mouse Sox2 supporting pluripotency is based on an evolutionally conserved activity of the Group B1 Sry-related high mobility group (HMG)-box (Sox) family
Since pluripotent stem cell population in developmental process could be regarded as the evolutional novelty in vertebrates, it could be regarded as a co-optional use of their evolutionally conserved function
Summary
Sox, and Sox can replace the function of Sox in mouse ES cells The mouse genome contains 20 Sox family members, which are divided into eight groups based on the amino acid sequence of the conserved HMG-box [18] (Additional file 1: Figure S1A). The Group G protein that rescues Sox self-renewal activity, contains a lysine at position 57 (Additional file 1: Figure S1A) This amino acid was previously reported to confer the differential activity of Sox and Sox in reprogramming somatic cells to iPS cells [22]. We confirmed that replacement of E57 with K in Sox conferred the ability to support self-renewal of Sox2-null ES cells (Additional file 2: Figure S2A-C) Together, these data indicate that a unique amino acid shared by Group B1 and Group G proteins primarily confers the self-renewal function of Sox family genes in ES cells. These results indicate that Hae ES cells retain pluripotency and are able to contribute to many lineages in the developing mouse embryo
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