Proteomics: Critical Similarity
Between Embryonic and iPS Cells
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 embryonic stem cells, they cannot be considered to be
identical.
In a study published today in Nature
Methods (Sunday, Sept. 11), researchers at the University
of Wisconsin-Madison report the first full measurement of the proteins made
by both types of stem cells. 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 is the first comprehensive
comparison of proteins in the two stem cell types, 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 protein 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."
Source:
University of Wisconsin-Madison
Contact:
Joshua Coon
Reference:
Proteomic and phosphoproteomic
comparison of human ES and iPS cells Douglas H Phanstiel, Justin Brumbaugh, Craig D Wenger, Shulan Tian, Mitchell D Probasco, Derek J Bailey, Danielle L Swaney, Mark A Tervo, Jennifer M Bolin, Victor Ruotti, Ron Stewart, James A Thomson & Joshua J Coon
Nature Methods 11 September 2011, doi:10.1038/nmeth.1699
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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/
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