SALL4 maintains self-renewal of porcine pluripotent stem cells through downregulation of OTX2

Abstract

Sall4 as one of the spalt family members contains several alternative splicing variants, which are differentially expressed and has a key role in maintaining pluripotent stem cells. However, the molecular features and function of SALL4 have not been well elucidated in porcine induced pluripotent stem cells (piPSCs). In this study, we identified SALL4 splice variants and found two SALL4 splicing variants through analysis of the porcine transcriptome data derived from piPSCs. SALL4A was only detected in piPSCs but SALL4B was globally expressed in porcine tissues and piPSCs. The level of SALL4B was significantly reduced when piPSCs differen-tiation occurred, however, the expression of SALL4A was not affected, indicating that SALL4B may be essential for the maintenance of piPSCs self-renewal. Overexpression of SALL4A and SALL4B in PEF cells could significantly stimulated expression of endogenous pluripotent genes, when SALL4B significantly promoted OCT4 expression. Conversely, SALL4A significantly promoted KLF4 expression. Additionally, both SALL4A and SALL4B could repress OTX2 promoter activity in a dose-dependent manner. Conversely, OTX2 also negatively regulated SALL4 expression. These observations indicate that a negative feedback regulatory mechanism may exist between SALL4 and OTX2, which is useful for the maintenance of the self-renewal of piPSCs.

Keywords

OTX2 / pluripotency / pig / SALL4 / transcription regulation

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Supplementary materials

The online version of this article at https://doi.org/10.15302/J-FASE-2017180 contains supplementary materials (Tables S1–S2; Figs. S1–S4).

Acknowledgements

This work was supported by the National Natural Science Foundation of China (31571521 and 31371505).

Compliance with ethics guidelines

Ning Wang, Sile Wang, Yaxian Wang, Yuanxing Cai, Fan Yang, and Huayan Wang declare that they have no conflicts of interests or financial conflicts to disclose.

This article does not contain any studies with human or animal subjects performed by any of the authors.

RIGHTS & PERMISSIONS

The Author(s) 2017. Published by Higher Education Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0)