The SOX transcription factors as key players in pluripotent stem cells

Abstract

Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), and induced PSCs (iPSCs) are able to self-renew and differentiate into a multitude of specialized cellular lineages. In these cells, the pluripotential identity is maintained by a group of transcription factors (TFs). Among these factors, SOX TFs play an essential role, not only in regulating pluripotency but also in mediating self-renewal and differentiation. Some SOX TFs are highly expressed in undifferentiated PSCs, while others are upregulated upon differentiation to promote specific lineage differentiation. Further roles of SOX factors in pluripotency are highlighted through their critical involvement in iPSCs generation. To perform these multiple functions and activities, SOX TFs are strongly associated with a complex regulatory network(s) that involves the binding of SOX factors to variant trans-acting partners to activate or suppress specific genes. Although, SOX2 has attracted special attention as a critical factor in maintaining PSCs characteristics and as an integral component that is required to reprogram somatic cells into pluripotency, new reports widely appreciated that other SOX TFs, such as SOX1, SOX3, or reengineered SOX7 and SOX17, can compensate for the absence of SOX2 and thus play a fundamental role during the reprogramming process and maintaining pluripotency. These findings indicate that the recent progress has greatly expanded our knowledge about the role of SOX factors in PSCs. Thus, in this review we summarize what is currently known about the roles of SOX factors in PSCs and their role in somatic cell reprogramming. Also, we intend to provide an update on their relationship with other factors in regulating the characteristics and early differentiation of PSCs.