What makes stem cells into perfect allrounders

June 27, 2017
Just a few days old embryonic cell clusters: with functional Pramel7 (left), without the protein (right) – the development of the stem cells remains stuck and the embyos die. Credit: Paolo Cinelli, USZ

Researchers from the University of Zurich and the University Hospital Zurich have discovered the protein that enables natural embryonic stem cells to form all body cells. In the case of embryonic stem cells maintained in cell cultures, this allrounder potential is limited. Scientists want to use this knowledge to treat large bone fractures with stem cells.

Stem cells are considered biological allrounders because they have the potential to develop into the various body cell types. For the majority of , however, this designation is too far-reaching. Adult stem cells, for example, can replace cells in their own tissue in case of injury, but a fat stem cell will never generate a nerve or liver cell. Scientists therefore distinguish between multipotent and the actual allrounders - the pluripotent .

Epigenetic marks determine potential for development

Differences exist even among the true allrounders, however. Embryonic stem cells that grow in laboratory cell cultures are in a different state than the found inside the embryos in the first days of development. In a study in the journal Nature Cell Biology, researchers led by Paolo Cinelli of the University Hospital Zurich and Raffaella Santoro of the University of Zurich have now demonstrated the mechanism by which natural allrounders differ from embryonic stem cells in cultures.

At the center of their discovery is a protein called Pramel7 (for "preferentially expressed antigen in melanoma"-like 7) found in the cells of embryonic cell clusters that are just a few days old. This protein guarantees that the genetic material is freed from epigenetic marks consisting of chemical DNA tags in the form of . "The more methyl groups are removed, the more open the Book of Life becomes," Cinelli says. Since any cell of the human body can develop from an embryonic stem cell, all genes have to be freely accessible at the beginning. The more a cell develops or differentiates, the stronger its genetic material is methylated and "sealed closed" again. In a bone cell, for example, only those genes are active that the cell requires for its function, the biochemist explains.

Protein is responsible for perfect pluripotency

Despite its short action period of just a few days, Pramel7 seems to play a vital role: When the researchers headed up by Cinelli and Santoro switched off the gene for this protein using genetic tricks, development remained stuck in the embryonic cell cluster stage. In the cultivated stem cells, on the other hand, Pramel7 is rarely found. This circumstance could also explain why the of these cells contains more methyl groups than that of natural embryonic cells - the perfect allrounders, as Cinelli calls them.

Using the stem cell function to regenerate bone tissue

His interest in stem cells lies in the hope of one day being able to help people with complex bone fractures. "Bones are great at regenerating and they are the only tissue that does not build scars," Paolo Cinelli says. The bone stumps must be touching, however, in order to grow together. When a bone breaks in multiple places and even through the skin, for example, in a motorcycle accident, the sections of bone in between are often no longer usable. For such cases, a replacement is required. His team is studying carrier materials that they want to populate with the body's own stem cells in the future. "For this reason, we have to know how stem work," Cinelli adds.

Explore further: New tools to study the origin of embryonic stem cells

More information: Urs Graf et al, Pramel7 mediates ground-state pluripotency through proteasomal–epigenetic combined pathways, Nature Cell Biology (2017). DOI: 10.1038/ncb3554

Related Stories

New tools to study the origin of embryonic stem cells

March 23, 2017

Researchers at Karolinska Institutet have identified cell surface markers specific for the very earliest stem cells in the human embryo. These cells are thought to possess great potential for replacing damaged tissue but ...

Vitamins and aminoacids regulate stem cell biology

February 16, 2017

An International Reserach Team coordinated by Igb-Cnr has discovered a key role of vitamins and amino acids in pluripotent stem cells. The research is published in Stem Cell Reports, and may provide new insights in cancer ...

Gene key for chemically reprogramming human stem cells

January 26, 2017

Scientists have discovered the gene essential for chemically reprogramming human amniotic stem cells into a more versatile state similar to embryonic stem cells, in research led by UCL and Heinrich Heine University.

New transitional stem cells discovered

April 16, 2015

Pre-eclampsia is a disease that affects 5 to 8 percent of pregnancies in America. Complications from this disease can lead to emergency cesarean sections early in pregnancies to save the lives of the infants and mothers. ...

Stem cells also rust

October 24, 2016

Oxygen in the air is well known to cause damaging rust on cars through a process known as oxidation. Similarly, a research group at Lund University in Sweden, has now identified that certain cells during embryonic development ...

How to detect and preserve human stem cells in the lab

January 22, 2016

Human stem cells that are capable of becoming any other kind of cell in the body have previously only been acquired and cultivated with difficulty. Scientists at the Max Delbrück Center for Molecular Medicine (MDC) in the ...

Recommended for you

Mammal long thought extinct in Australia resurfaces

December 15, 2017

A crest-tailed mulgara, a small carnivorous marsupial known only from fossilised bone fragments and presumed extinct in NSW for more than century, has been discovered in Sturt National Park north-west of Tibooburra.

Finding a lethal parasite's vulnerabilities

December 15, 2017

An estimated 100 million people around the world are infected with Strongyloides stercoralis, a parasitic nematode, yet it's likely that many don't know it. The infection can persist for years, usually only causing mild symptoms. ...

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.