Future of iPSC

Yamanaka Factors

Back in 2006, Shinya Yamanaka discovered that you could turn normal somatic cells into pluripotent stem cells with the overexposure of 4 growth genes: OCT4, Sox2, c-MYC, KLF4. These four growth genes were found in embryonic stem cells and proved to show pluripotency in regular cells with over-expression. These four transcription factors are called Yamanaka Factors, and they are our current validated method of creating induced pluripotent stem cells (iPSC). But there are problems that have arisen from this type of reprogramming:

1) Oncogenic Transformation

  • Oct-4 is an octamer binding transcription factor that is expressed in undifferentiated cells, that deals with the self-renewal property of stem cells.
  • Sox2 is a sex-determining region Y box 2, which means that it is a transcription factor that also deals with self-renewal but also pluripotency.
  • KLF4 is a kruppel-like factor, which is a transcription factor that deals with proliferation and differentiation traits in stem cells.
  • C-Myc is part of a family of regulatory genes, this transcription factor is also expressed in cancer for its proliferation ability..

2) Efficiency

Not only do these four transcription factors show a high probability for tumor growth, but they also take a long time to actually create.

What is Deterministic Reprogramming?

Multiple studies have shown alternative reprogramming protocols where rapid and up to 100% reprogramming efficiency can be obtained within a relatively short period. These types of methods are called deterministic reprogramming while using transcription factors and such are called stochastic processes.

  • Gatad2a is a gene that facilitates the deterministic reprogramming methods like the disruption of the Mbd3 gene that allows the ESC to remain in its pluripotency state
  • Mbd3/NuRD complex is the gene that turns off the pluripotency state in ESC, in order for them to differentiate into different types of somatic cells
  • OKSM is the Yamanaka factors that are used to create the pluripotency in these somatic cells

Retrovirus with infected β cells

Implications

Deterministic reprogramming methods are in the testing stage, where the are running clinical trials or have run trials very few times. But the implications for newer and more efficient methods of reprogramming stem cells are huge.

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Valmik Rao

Valmik Rao

Just a 16-year-old trying to solve the world’s biggest problems…