A Study of Protein Synthesis In Stem Cells Conducted For The First Time

By Liisa Vexler

Scientists at the Children's Medical Center Research Institute, UT Southwestern Medical Center, Texas, have conducted a breakthrough piece of research into protein synthesis in adult stem cells. The research, previously not possible to conduct, has linked certain cancers with mutations affecting protein synthesis.

The process used an antibiotic called puromycin, in modified form, to aid in measuring the quantity of protein synthesized in the body. Research revealed that protein is produced at a different rate per hour for different types of blood cells. It was also noted that much lower amounts of protein are synthesized by stem cells than other cells (blood-forming). The research, conducted on mice, concluded that when ribosome, a genetic mutation involved in making protein, was present the production of protein in stem cells diminished by 30%. Conversely, in another experiment the tumor-suppressor gene P-ten was removed in an attempt to increase protein synthesis, resulting in an impairment of stem cell function. These findings conclude that protein synthesis for blood forming stem cells needs to be well regulated or else they will not function efficiently. A member of the team, Dr. Morrison, observed to his amazement that breeding Pten mutant mice with ribosomal mutant mice returned stem cell function to normal, leading to either a complete block or delay on the development of Leukaemia. Dr. Morrison is of the view that, all of this happened because protein production in stem cells was returned to normal. It was as if two wrongs made a right. The findings are thought to open the door to a number of similar tests for the many kinds of cells in the human body, making it possible to study protein synthesis for each. The research is thought to be important for understanding the differences in the rates and ways that protein in synthesized in cells and what this means for cellular survival.

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A Study of Protein Synthesis In Stem Cells Conducted For The First Time

Researchers find stem cells remember prior substrates

6 hours ago by Bob Yirka Mesenchymal stem cell displaying typical ultrastructural characteristics. Credit: Robert M. Hunt/Wikipedia

(Phys.org) A team of researchers working at the University of Colorado has found that human stem cells appear to remember the physical nature of the structure they were grown on, after being moved to a different substrate. In their paper published in the journal Nature Materials, the researchers describe how they grew human stem cells on different substrates. In so doing, they discovered that the stem cells continued to express certain proteins related to a substrate even after its hardness was changed.

Scientists have known for some time that stem cells respond to their environment as they growthose grown on hard material, such as glass or metal for example, are more amenable to growing into bone cells. In this new effort, the researchers sought to discover if changes to a stem cell brought about by environment are retained if the stem cell is moved to a different environment.

To find out, the researchers used mesenchymal cells which are known to be able to grow into almost any human body part. They placed the stem cells on a stiff substrate then moved them to one less stiff over differing numbers of days. In so doing, they found that the longer the cells were left on the stiff substrate the more a protein connected to bone growth (RUNX2) was expressed. Conversely, cells that were first placed on a soft surface and subsequently moved to a hard surface demonstrated a tendency to develop either bone or adipogenic tendencies.

In another experiment, the researchers applied the stem cells to a substrate coated with a phototunable hydrogelit grows softer when exposed to lightusing it allowed for changing the stiffness of the substrate without having to move the cells. Using this approach the team found that if the cells were allowed to grow on the gel in its stiff state, for just one day, switching to a soft state caused the expression of RUNX2 to cease immediately. When they allowed the cells to grow for ten days on the stiff base, however, before switching to a soft one, expression of RUNX2 continued for another ten days before finally ceasing. This shows, the researchers contend, that stem cells have a memory component that is not yet understood.

The researchers note that their findings could be applied to other stem cell research areas such as cases where unintentional consequences may be arising in experiments due to the stiffness of the substrate in which they are being grown. It also raises the question of whether other environmental factors might be impacting cell growth and if so, if they have a memory component as well.

Explore further: Heart cells respond to stiff environments

More information: Mechanical memory and dosing influence stem cell fate, Nature Materials (2014) DOI: 10.1038/nmat3889

Abstract We investigated whether stem cells remember past physical signals and whether these can be exploited to dose cells mechanically. We found that the activation of the Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) as well as the pre-osteogenic transcription factor RUNX2 in human mesenchymal stem cells (hMSCs) cultured on soft poly(ethylene glycol) (PEG) hydrogels (Young's modulus E ~ 2 kPa) depended on previous culture time on stiff tissue culture polystyrene (TCPS; E ~ 3 GPa). In addition, mechanical dosing of hMSCs cultured on initially stiff (E ~ 10 kPa) and then soft (E ~ 2 kPa) phototunable PEG hydrogels resulted in either reversible orabove a threshold mechanical doseirreversible activation of YAP/TAZ and RUNX2. We also found that increased mechanical dosing on supraphysiologically stiff TCPS biases hMSCs towards osteogenic differentiation. We conclude that stem cells possess mechanical memorywith YAP/TAZ acting as an intracellular mechanical rheostatthat stores information from past physical environments and influences the cells' fate.

Journal reference: Nature Materials

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Researchers find stem cells remember prior substrates

Nobel laureate calls handing of stem cell research data 'sloppy'

The Nobel Prize-winning head of a Japanese institute whose scientists' work on stem cells was hailed as a game-changer in the field of medical biology called the lead researcher's handling of the data "extremely sloppy" and "irresponsible".

Two papers published in the journal Nature in January detailed a simple way to reprogram mature animal cells back into an embryonic-like state that allows them to generate many types of tissue, offering hope for a simpler way to replace damaged cells or grow new organs in humans.

But other scientists have been unable to replicate the research's results since then and there have been indications of problems with its data and images.

"The problem here is one immature researcher collected a huge amount of research data, and her handling of data was extremely sloppy and irresponsible," president of Japanese research institute RIKEN Ryoji Noyori told a news conference.

"I would like to offer my apology for the Nature articles, having brought into question the credibility of the science community," said Noyori, bowing deeply.

Noyori, who won a Nobel prize for chemistry in 2001, was referring to Haruko Obokata, 30, a lead author of the papers who became an instant celebrity in Japan after they were published.

A written statement from Obokata and two other RIKEN researchers made available at the news conference said they are discussing the possible withdrawal of the papers with other co-authors.

Another scientist on the team, Teruhiko Wakayama of the University of Yamanashi, has already called for the papers to be withdrawn.

"It is no longer clear what's right," Wakayama told public broadcaster NHK on Monday.

The news conference was called to release the interim findings of investigation on the controversy by a panel of experts from within and outside RIKEN.

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Nobel laureate calls handing of stem cell research data 'sloppy'