Critical similarity between two types of do-it-all stem cells revealed in new study

Sep 11, 2011 by David Tenenbaum

Ever since human induced pluripotent stem cells were first derived in 2007, scientists have wondered whether they were functionally equivalent to embryonic stem cells, which are sourced in early-stage embryos.

Both cell types have the ability to differentiate into any cell in the body, but their origins – in embryonic and adult tissue – suggest that they are not identical.

Although both cell types have great potential in basic biological research and in cell- and tissue-replacement therapy, the newer form, called IPS cells, have two advantages. They face less ethical constraint, as they do not require embryos. And they could be more useful in cell replacement therapies: growing them from the patient's own cells would avoid immune rejection.

But until IPS cells are proven to have the same traits as , they cannot be considered to be identical.

In a study published today (Sunday, Sept. 11), researchers at the University of Wisconsin-Madison report the first full measurement of the proteins made by both types of . In a study that looked at four embryonic stem cells and four IPS cells, the proteins turned out to be 99 percent similar, says Joshua Coon, an associate professor of chemistry and biomolecular chemistry who directed the project.

"We looked at RNA, at proteins, and at structures on the proteins that help regulate their activity, and saw substantial similarity between the two stem-cell types," he says.

Proteins are complex molecules made by cells for innumerable structural and chemical purposes, and the new study measured more than 6,000 individual proteins using highly accurate mass spectrometry, a technique that measures mass as the first step of identifying proteins.

The study in Nature Methods, published online, is the first comprehensive comparison of proteins in the two stem , says Doug Phanstiel, who is now at Stanford University, and worked with Justin Brumbaugh on the project as graduate students at UW-Madison.

"From a biological standpoint, what is novel is that this is the first proteomic comparison of embryonic stem cells and IPS cells," says Phanstiel, referring to the study of which proteins a cell produces.

In essence, every cell in the body has the genes to make any protein the body might need, but cells make only the proteins that further their own biological role. Cells regulate the formation and activity of proteins in three ways: first, by controlling the production of RNA, a molecule that transfers the DNA code to protein-making structures; second, by controlling the quantity of each protein made; and third, by adding structures to the protein that regulate when it will be active.

The new study measured each of these activities, Phanstiel says.

"And because we compared four lines of each type of stem cell, and the comparisons were run three times, the statistics are extremely robust," he adds.

The new report, Coon says, suggests that embryonic stem cells and IPS cells are quite similar. According to some measurements, the protein production of an embryonic stem cell was closer to that of an IPS cell than to a second embryonic stem cell.

The ability to measure proteins in such detail emerged from improved ways to measure mass, Coon says.

"New technical developments in both our ability to measure a protein's mass – accurate to the third or fourth decimal place – and to compare the proteins from up to eight different cell lines at a time -- permitted this important comparison for the first time," says Coon.

The study is not the last word in determining the similarity of the two types of pluripotent stem cells, says Coon, who worked with UW-Madison stem-cell pioneer James Thomson, on the project.

Because clinical uses of either type of stem cells will require that they be transformed into more specialized cells, researchers still need to know more about production after a stem cell is differentiated into, for example, a neuron or heart muscle cell.

This technology, Coon says, "is now well-positioned to study how closely molecules contained in these promising cells change after they are differentiated into the cells that do the work in our bodies – a critical next step in regenerative medicine."

Explore further: Fungus deadly to AIDS patients found to grow on trees

Related Stories

Stem cells reverse disease in a model of Parkinson's disease

May 16, 2011

In a new study to be published in the Journal of Clinical Investigation, researchers compared the ability of cells derived from different types of human stem cell to reverse disease in a rat model of Parkinson disease and id ...

Cells derived from different stem cells: Same or different?

May 02, 2011

There are two types of stem cell considered promising sources of cells for regenerative therapies: ES and iPS cells. Recent data indicate these cells are molecularly different, raising the possibility that cells derived from ...

Recommended for you

Researchers discover new strategy germs use to invade cells

Aug 20, 2014

The hospital germ Pseudomonas aeruginosa wraps itself into the membrane of human cells: A team led by Dr. Thorsten Eierhoff and Junior Professor Dr. Winfried Römer from the Institute of Biology II, members of the Cluster ...

Progress in the fight against harmful fungi

Aug 20, 2014

A group of researchers at the Max F. Perutz Laboratories has created one of the three world's largest gene libraries for the Candida glabrata yeast, which is harmful to humans. Molecular analysis of the Candida ...

How steroid hormones enable plants to grow

Aug 19, 2014

Plants can adapt extremely quickly to changes in their environment. Hormones, chemical messengers that are activated in direct response to light and temperature stimuli help them achieve this. Plant steroid ...

User comments : 6

Adjust slider to filter visible comments by rank

Display comments: newest first

XQZME
1 / 5 (1) Sep 11, 2011
Please explain:
According to some measurements, the protein production of an embryonic stem cell was closer to that of an IPS cell than to a second embryonic stem cell.

If a protein from Embryonic Stem Cell (ESC) A differs from that produced by IPS X by 1% but differs from the protein produced by ESC B by 5%, then wouldnt the protein produced by ESC B differ from the protein produced by IPS X by 4% to 6%?
nanotech_republika_pl
not rated yet Sep 11, 2011
I think that these 4 hES cells (ESC) were taken from four different mutated stem cells, that differ enough from each other that they can be considered as if they come from four different people. In fact, in the paper itself they say that they took the lines from four lines of HeLa cell, if I understand right.

Quoting from the paper: "four ESC lines (H1, H7, H9 and H14) and four iPSC lines (DF4.7, DF6.9, DF19.11 and DF19.7)."

I don't know what the DF means. I wonder however, how do you get an iPS cell from a ESC cell? I am newbie in the field. But I would imagine that if run an experiment I would find a stem cell in a human bone marrow and took some other cell from a skin of the same person and then convert that skin cell to iPS. This way I would know that they were created with the same DNA, but with different epigenetic modfications (like methylation, or acetylation) (say, by 1%).
nanotech_republika_pl
not rated yet Sep 11, 2011
... and of course the stem cell from bone marrow is not an ESC. So I don't know. This all is puzzle to me. Anybody please explain?
ArtflDgr
1 / 5 (4) Sep 11, 2011
But until IPS cells are proven to have the same traits as embryonic stem cells, they cannot be considered to be identical.

funny... they think of other cells as types, and assume they are the same when they are not... so this higher standard for just those cells is because they want a use for fetuses for political reasons.

whatever_dude
5 / 5 (2) Sep 12, 2011
@ArtflDgr: Shut up. The extra controls are necessary because of the moral scrutiny on embryonic cells. What is your problem?
ArtflDgr
1 / 5 (2) Sep 12, 2011
my problem?

nothing. i am a applications engineer working in a research hospital and with a top geneticist... a very famous one too..

the point is that you dont need to harvest fetal cells from dead children unrealized. the preservation of that, as in 1917 soviet union (where my family is from), is more important than even science... (to those that follow that)

we are working on a redefinition of the blue print model, which is quite wrong the way its given lipservice but never put down.

the researcher i am working with was originally not an academic, and like me, and experience, know the farce of the political games mapped OVER the science. as with a man named lysenko (turning science into ideological religion).

technically i dont follow the religion of the religious prophet from 1850 names Marx, of whom most of what he predicted was very wrong... (but since when is it a problem to beleive wrong and let darwin handle it over time?)