What is Pluripotency?
Pluripotency is defined as the ability of a stem cell to differentiate into any cell within the three germ layers (endoderm, mesoderm, and ectoderm).
Embryonic stem cells can develop into any type of cell in the human body. As an embryo develops, genes which are involved in pluripotency are expressed less, leading to increased lineage commitment and differentiation.
3d illustration of the making of induced pluripotent stem cells (iPSCs). Image Credit: Meletios Verras / Shutterstock Genes Involved in Pluripotency
Three main transcription factors involved in the maintenance of pluripotency are referred to as the golden triangle of transcription activity: Octamer-binding transcription factor (Oct4), Sex-determining region Y-box 2 (SOX2) and Nanog. Oct4 was first identified for the formation of the inner pluripotent mass of cells within a blastocyst during the development of an embryo. SOX2 was then found to heterodimerize with Oct4 and activate downstream genes involved in pluripotency. Finally, a downstream homeobox protein target of these two proteins was identified, NANOG. These proteins are all master transcription factors, vital in maintaining pluripotency and activating differentiation, stimulating each other to form a positive feedback loop.
Stimulation of Differentiation
The regulation of pluripotency is controlled through a signaling pathway which maintains the stem-ness of a cell until it differentiates. Differentiation is stimulated through the epidermal growth factor and other proteins, while pluripotency is maintained and stimulated through two signaling proteins: bone morphogenesis protein (BMP) and leukemia inhibitory factor (LIF). These signaling proteins maintain pluripotency by promoting the expression of the core pluripotency genes and repressing genes involved in differentiation.
Other Factors Involved in the Maintenance of Pluripotency
There are many other genes that are involved in the maintaining pluripotent cells. For example, the polycomb family proteins and Ronin are vital to maintain chromatin. They stimulate the compaction and methylation of chromatin and prevent gene expression to maintain epigenetic silencing of genes involved in differentiation. Nurd is another transcription factor which is vital for the development of cells. This protein directly controls the transcription of pluripotent genes and prevents their transcription, allowing the cell to commit to a lineage. Therefore, this protein must be maintained at low levels in pluripotency. There are also many other genes which are involved to maintain pluripotent cells, such as KLF4, REX1, SSEA4, TRA-1-60, AND TRA-1-81.
Genes and Induced Pluripotency
The work of Shinya Yamanaka in Kyoto University (Japan) in 2006 disproved the opinion that the lineage commitment and development of an adult cell is irreversible. This study identified that pluripotency-related genes (OCT4, SOX2, Klf4, and Myc) in adult cells reprogrammed the cells and produced induced pluripotent cells (iPS) that can be used to form any type of cell in the body. This exciting scientific development holds promise for future disease modeling and treatment. While embryonic stem cells have many tricky ethical issues, these cells do not have any ethical concerns and can be used to form any cell in the body. These cells will also be autonomous to the patient, reducing the chances of rejection following transplant. However, iPS cells have not been tested in clinical trials.