SOX2 Protein at Every Age: Embryonic Stem Cells, Pluripotency, and Plasticity

SOX2 belongs to the Sox family of proteins which play essential roles in cell differentiation, development, and organogenesis.

Contributed by Amy Archuleta

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SOX2 was first identified in the 1990s.

The discovery of the SOX family of proteins started in 1990 while investigating the genetic mechanisms involved in sex determination. SRY (Sex-Determining Region Y) protein was the first family member identified, and the SOX family got its name due to its similarity to the SRY gene, which is the master regulator of male sex determination in mammals. SOX2, short for SRY (Sex-Determining Region Y)-Box 2, was identified shortly thereafter, and in 1994 the human SOX2 gene was cloned and characterized. This discovery marked a significant step in understanding the role of SOX2 as a transcription factor and its involvement in embryonic development, particularly in the formation of the central nervous system.

A transcription factor, SOX2 aids in the embryonic formation of the central nervous system and neural progenitor cells.

Transcription factors are proteins that bind to specific DNA sequences and through RNA ultimately guide the synthesis of proteins. The DNA binding domain encoded by the Sox gene family contains a conserved high-mobility group (HMG) box, to which all family members, including SOX2 can bind. This sequence is often found in the regulatory regions of genes associated with pluripotency.

During embryonic development, SOX2 is expressed in the inner cell mass of the blastocyst. This expression is crucial for the subsequent development of the embryo’s nervous system. For example, SOX2 is instrumental in the formation of neural progenitor cells - precursor cells that give rise to the various cell types of the nervous system. Its expression is particularly high in these cells during neural development.

SOX2 helps to maintain the pluripotency of embryonic stem cells, allowing them to differentiate.

The ability of SOX2 to maintain pluripotency is a critical aspect of its function. Transcription factors Oct4 and Nanog work with SOX2 to create the OSN network, which influences the expression of genes that preserve the undifferentiated state of embryonic stem cells. This network allows for the self-renewal of pluripotent stem cells and maintains the potential of the stem cells to differentiate into any cell type in the body.

The importance of SOX2 continues into adulthood.

In adult tissues, SOX2 aids in neural tissue regeneration and repair, as well as the maintenance of adult neural stem cells and their ability to develop into different specialized cell types, essential for neural plasticity. SOX2 participates in tissue-specific differentiation in adult tissues, ensuring that cells maintain their specialized functions. This is critical for the maintenance of tissue integrity and function throughout adulthood. Also expressed in the respiratory epithelium of the lungs, SOX2 is involved in maintaining tissue homeostasis.

SOX2 is implicated in many different disease states.

Mutations or dysregulation of SOX2 have been linked to a range of neurological diseases, including neurodevelopmental disorders like aniridia (Matsushima 2011), and optic nerve hypoplasia and septo-optic dysplasia (McCabe 2010). SOX2 has also be implicated in certain brain tumors, particularly in gliomas, where its dysregulation can contribute to uncontrolled cell proliferation (Mansouri 2016).

Potential therapeutic applications in regenerative medicine.

There are several potential therapeutic applications of SOX2, particularly in the field of regenerative medicine. The ability of SOX2 to influence cell fate and differentiation suggests options for reprogramming adult cells into a pluripotent state, holding promise for tissue repair and regeneration.

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