Single factor converts adult stem cells into embryonic-like stem cells

February 5, 2009

The simple recipe scientists earlier discovered for making adult stem cells behave like embryonic-like stem cells just got even simpler. A new report in the February 6th issue of the journal Cell, a Cell Press publication, shows for the first time that neural stem cells taken from adult mice can take on the characteristics of embryonic stem cells with the addition of a single transcription factor. Transcription factors are genes that control the activity of other genes.

The discovery follows a 2006 report also in the journal Cell that showed that the introduction of four ingredients could transform differentiated cells taken from adult mice into "induced pluripotent stem cells" (iPS) with the physical, growth, and genetic characteristics typical of embryonic stem cells. Pluripotent refers to the ability to differentiate into most other cell types. The same recipe was later shown to work with human skin cells as well.

Subsequent studies found that the four-ingredient recipe could in some cases be pared down to just two or three essential ingredients, said Hans Schöler of the Max Planck Institute for Molecular Biomedicine in Germany. "Now we've come down to just one that is sufficient. In terms of the biology, it's really quite amazing."

The discovery sheds light on centuries-old questions about what distinguishes the embryonic stem cells that give rise to egg and sperm from other body cells, Schöler said. It might also have implications for the use of reprogrammed stem cells for replacing cells lost to disease or injury.

Other researchers led by Shinya Yamanaka showed that adult cells could be reprogrammed by adding four factors - specifically Oct4, Sox2, Klf4, and c-Myc. Recently, Schöler and his colleagues demonstrated that Oct4 and Klf4 are sufficient to induce pluripotency in neural stem cells.

By omitting Klf4 in the new study, they have now established that Oct4 is the "driving force" behind the conversion of the neural stem cells into iPS cells. The lone transcription factor is not only essential, but it is also sufficient to make neural stem cells pluripotent.

Those cells, which Schöler's team calls "1F iPS" can differentiate into all three germ layers. Those primary germ layers in embryos eventually give rise to all the body's tissues and organs. Not only can those cells efficiently differentiate into neural stem cells, heart muscle cells, and germ cells, they show, but they are also capable of forming tumors when injected under the skin of nude mice. Those tumors, or teratomas, contain tissue representing all three germ layers. When injected into mouse embryos, the 1F iPS cells also found their way into the animals' developing organs and were able to be transmitted through the germ line to the next generation, they report.

The results show that adult stem cells can be made pluripotent without c-Myc and Klf4, both of which are "bona fide" oncogenes that can help turn normal cells into cancer cells, Schöler said. Limiting the number of factors is also a bonus because it means fewer genes must be inserted into the genome, where they can potentially have detrimental effects.

"Strikingly, Oct4 alone is sufficient to induce pluripotency in neural stem cells, which demonstrates its crucial role in the process of reprogramming…" the researchers concluded. "Future studies will show whether other sources of neural stem or progenitor cell populations such as mouse or human bone marrow-derived mesenchymal stem cells or dental pulp can be reprogrammed to iPS cells and whether expression of Oct4 can be induced by non-retroviral means, a prerequisite for the generation of iPS cells of therapeutic value."

Source: Cell Press

Explore further: Phenogenetic map created for stem cells models of neurological diseases

Related Stories

New findings explain how UV rays trigger skin cancer

October 18, 2017

Melanoma, a cancer of skin pigment cells called melanocytes, will strike an estimated 87,110 people in the U.S. in 2017, according to the Centers for Disease Control and Prevention. A fraction of those melanomas come from ...

Inflammation trains the skin to heal faster

October 18, 2017

Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

Recommended for you

Metacognition training boosts gen chem exam scores

October 20, 2017

It's a lesson in scholastic humility: You waltz into an exam, confident that you've got a good enough grip on the class material to swing an 80 percent or so, maybe a 90 if some of the questions go your way.

Carbon coating gives biochar its garden-greening power

October 20, 2017

For more than 100 years, biochar, a carbon-rich, charcoal-like substance made from oxygen-deprived plant or other organic matter, has both delighted and puzzled scientists. As a soil additive, biochar can store carbon and ...

Dawn mission extended at Ceres

October 20, 2017

NASA has authorized a second extension of the Dawn mission at Ceres, the largest object in the asteroid belt between Mars and Jupiter. During this extension, the spacecraft will descend to lower altitudes than ever before ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.