Protein Essential For Constructing Stem Cells IDENTIFIED!

Protein Essential For Constructing Stem Cells IDENTIFIED!

NKX3-1 is the protein important for the production of iPS cells (Induced Pluripotent stem cells), say researchers at the School of Medicine. The NKX3-1 protein can substitute one of the four proteins identified by Shinya Yamanaka, MD, Ph.D. in 2007. It will be sufficient to prod mature cells to become iPS cells using the Reprogramming technique.

This discovery may introduce new ways to generate iPS cells in the lab. Helen Blau, Ph.D., professor of microbiology and immunology said that they used a unique laboratory model for reprogramming to identify the NKX3-1 protein. It appeared after two hours of the reprogramming initiation and then disappeared. But, it’s critical to reprogramming.

Yamanaka won the Nobel Prize for introducing the ability to reprogram mature cells into pluripotent stem cells by adding just four proteins.

The Research Leads To A Safer Reprogramming of Stem Cells

Exposing mature cell types to four Yamanaka factors—Oct4, Sox2, cMyc, and Klf4 makes them behave like stem cells. They began expressing Oct4 on their own. However, cMyc and Oct4 oncogenes can cause cancers when overly expressed in normal stem cells. The proper knowledge of reprogramming will help find new ways to generate

stem cells for safe use.

Thach Mai, Ph.D., the lead author of the research. To fix it, Mai considered a cell fusion model. Blau used this model in the 1980s to demonstrate that specialized human cells could express muscle-specific genes when joined with mouse muscle fibers. In the new study, Mai fused fibroblasts human skin cells to mouse embryonic stem cells. The fused cells, heterokaryons, made it possible for Mai to track gene expression and DNA modification within the first 24 hours of reprogramming.

The researchers found that NKX3-1 is expressed within nearly two hours of the reprogramming initiation but rapidly dissipates. Blocking the protein’s expression will forbid the Yamanaka factors to reprogram the human fibroblasts. It suggests the criticality of NKX3-1 in the conversion of adult cells to stem cells. Also, NKX3-1 can replace Oct4 to reprogram cells without compromising its competence.

Finally, they showed that NKX3-1 expression was important to trigger the cells’ expression of their own Oct4 protein and to promote other genetic changes that facilitate reprogramming.

Exploring Deeper

Now Blau has joined professor Anshul Kundaje, Ph.D. to research on reprogramming to pluripotency with the use a multipronged “omics-based” technique. They will study the pathways that make reprogramming completely change a cell’s fate.