Question

In a landmark paper published in 2006, Shinya Yamanaka discovered a minimal number of transcription factors that could transform somatic cells into pluripotent stem cells (iPSC). The discovery of the “Yamanaka factors” was a major break-through in stem cell biology and has revolutionized regenerative medicine. What was the major observation from previous studies that lead Yamanaka (and others) to believe that it would be possible for a somatic cell to be re-programmed back into a pluripotent stem cell?

Answer 1

Shinya Yamanaka published his paper on conversion of any somatic cell into  pluripotent stem cells (iPSC) in 2006 where he wrote about his work that certain transcription factors are there which are causing this conversion.

-These transcription factors are Myc, Oct 3/4, Sox 2 and Klf 4 .

-Yamanaka and his collegues did experiment on mice fibroblast usinf retroviral factors.

-Pluripotency means a phenomenon through which any cell can be converted into any adult cell type. Any somatic cell can be induced to pluripotency except the extraembryonic cells which are forming the plcenta.

- Pluripotent stem cell divides to form either two new stem cells or one stem cell and a daughter cell. the daughter cell matures, differentiates and acquires a special function.

-John Gurdon through his nuclear tranplantation technique revealed that the nucleus of mature and differentiated cells can induce pluripotency in any somatic cell to produce an entire organism or a new organ. But it also depends upon the expression of the genetic information.

-Yamanaka was influenced from the work of Gurdon and started thinking that

• What makes a stem cell a stem cell?
• How the sheep dolly is cloned?
• Why matured cells cannot be transformed to pluripotent stem cells?

- All these questions fascinated Yamanaka to work on pluripotent stem cells.

-Yamanaka wanted to work with the research lab of the US after reading about the genetic modification of the mice where the genes are removed and are either replaced or modified. He found that a protein named Nat1 is responsible for the conversion and differentiation of stem cells into matured cells.

- Yamanaka in his work also stated that cell differentiation doesnot mean that the genome is also modified permanently, rather the genome contains certain active genes which can induce pluripotency.