A team of researchers led by Michigan State University biochemist and molecular biologist Amy Ralston has discovered a new kind of stem cell — induced extraembryonic endoderm stem (iXEN) cells.
Morphology of iXEN cells is similar to that of blastocyst-derived XEN cells. Image credit: Anthony Parenti et al.
“Other scientists may have seen these cells before, but they were considered to be defective, or cancer-like. Rather than ignore these cells that have been mislabeled as waste byproducts, we found gold in the garbage,” said team member Anthony Parenti, also from Michigan State University.
A great deal of stem cell research focuses on new ways to make and use pluripotent stem cells.
Pluripotent stem cells can be created by reactivating embryonic genes to reprogram mature adult cells. Reprogramming mature cells into induced pluripotent stem (iPS) cells, allows them to become malleable building blocks that can morph into any cell in the body.
Prior to the discovery of reprogramming, scientists developed pluripotent stem cells from embryos. However, the embryo produces not only pluripotent stem cells, but also so-called extraembryonic endoderm stem (XEN) cells.
While pluripotent stem cells produce cells in the body, XEN cells produce extraembryonic tissues that play an essential but indirect role in fetal development.
Parenti, Dr. Ralston and their colleagues speculated that if the embryo produces both pluripotent and XEN cells, this might also occur during reprogramming.
The ‘Eureka!’ moment came when Parenti discovered colonies of iXEN cells popping up like weeds in his iPS cell cultures.
Using mice models, he and co-authors spent several months proving that these genetic weeds are not cancer-like, as previously suspected, but in fact, a new kind of stem cell with desirable properties.
Even more surprising, the team found that by inhibiting expression of XEN genes during reprogramming, they could decrease production of iXEN cells and increase production of iPS cells.
“Nature makes stem cells perfectly, but we are still trying to improve our stem cell production,” Parenti said.
“We took what we learned by studying the embryo and applied it to reprogramming, and this opened up a new way to optimize reprogramming.”
“The next steps will involve seeing if this process occurs in human cells.”
“XEN cells have characteristics that pluripotent stem cells do not have,” Dr. Ralston said. “Because of those traits, iXEN cells can shed light on reproductive diseases.”
“If we can continue to unlock the secrets of iXEN cells, we may be able to improve induced pluripotent stem cell quality and lay the groundwork for future research on tissues that protect and nourish the human embryo.”
Details of the discovery are published in the journal Stem Cell Reports.
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Anthony Parenti et al. OSKM Induce Extraembryonic Endoderm Stem Cells in Parallel to Induced Pluripotent Stem Cells. Stem Cell Reports, published online March 3, 2016; doi: 10.1016/j.stemcr.2016.02.003
