Characterization of novel alternative splicing variants of Oct4 gene expressed in mouse pluripotent stem cells

Oct4 is an important transcription factor for maintaining self-renewal and pluripotency of pluripotent stem cells (PSCs). Human OCT4 can be alternatively spliced and generate OCT4a, OCT4b, and OCT4b1. In this study, we discovered the novel Oct4 variants of Oct4b' and Oct4b1-3 in mouse PSCs for the first time. The expression of Oct4b variants, especially for Oct4b', was down regulated along with the downregulation of Oct4a when stem cells were differentiated. We also found four Oct4 translational products that were differentially expressed in mouse PSCs under the different culture conditions. The constructs of Oct4b2 and Oct4b3 could be alternatively spliced into Oct4b and Oct4b' when constructs were transiently transfected in NIH3T3 cells. Oct4b' encoded a 189 aa protein, and Oct4b could generate three distinct proteins including Oct4b-246aa, Oct4b-221aa, and Oct4b-189aa. The Oct4b variants could be alternatively translated in different type cells under the control of internal ribosome entry site (IRES) element that is within 5' upstream sequence of Oct4b. These findings provide new insights into reconsidering Oct4 variants expression and its additional role in maintaining the pluripotency of stem cells.