New stem cell could offer new ways to study birth defects

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Tony Parenti, MSU Ph.D student in cell and molecular biology

You never know what you are going to find in the trash. For a group of intrepid researchers at Michigan State University their discovery could lead to new ways of studying birth defects.

Because what they found in what’s normally considered cellular trash was a new kind of stem cell.

iXEN cell

The cell is called an induced extraembryonic endoderm stem (iXEN) cell. The team’s findings are reported in the journal Stem Cell Reports and here’s how lead author Tony Parenti described what they found:

“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.”

Here’s the backstory. For years, researchers viewed embryonic stem cells as the “gold standard” for pluripotent cells—the type that can differentiate into all cell types in the body.

But studies in mice show that, in addition to producing pluripotent stem cells, the mouse embryo also generates extraembryonic endoderm, or XEN, cells. For a long time, scientists believed XEN cell gene expression influenced pluripotent stem cells, but they typically dismissed XEN cells as cancer‑like byproducts of embryonic development.

Searching through the trash

And that’s how things stayed until the MSU research team noticed that XEN‑like cells appeared every time they created induced pluripotent stem (iPS) cells—man‑made equivalents of embryonic stem cells that can turn into any cell type but are reprogrammed from adult cells.

They set out to understand how important these “induced,” or iXEN, cells were to iPS cell development. When they reprogrammed adult mouse cells into iPS cells, they consistently saw colonies of iXEN cells in the cultures.

Their first goal was to determine whether these iXEN cells were cancer‑causing, as many believed. After six months of work, they showed that the cells are not cancerous in culture and confirmed that they represent a new type of stem cell.

Next, they examined how endodermal genes contribute to iXEN cell formation. When they reduced endodermal gene expression, the number of iXEN cells dropped by half. At the same time, the number of iPS cells increased significantly.

Competitors not collaborators

Parallel pathways that produce pluripotent cells and XEN cells compete during reprogramming rather than support one another. By suppressing one pathway, they were able to boost the other. To their surprise, this led to a more efficient way to generate iPS cells.

While discovering a new type of stem cell is exciting, there’s a catch: scientists still don’t know whether XEN cells exist in humans. Even so, this finding gives researchers new tools to explore that question.

Amy Ralston, a co‑author of the study, explained in a news release:

“It’s a missing tool that we don’t have yet. It’s true that XEN cells have characteristics that pluripotent stem cells do not have. 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. We may be able to lay the groundwork for future research on tissues that protect and nourish the human embryo.”

The discovery of anything new usually meets healthy skepticism at first. In science, that’s a good thing. But so far the Twitterverse and media outlets seems to share in the excitement about this discovery.

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Trash talking and creating a stem cell community

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