Nav: Home

Embryos remember the chemicals that they encounter

November 08, 2018

We all start out as a clump of identical cells. As these cells divide and multiply, they gradually take on distinct identities, acquiring the traits necessary to form, for instance, muscle tissue, bone, or nerves. A recent study from Rockefeller scientists offers new insight into how these cellular identities are cultivated over the course of development.

According to the study, published in eLife, cells retain a memory of the chemical signals to which they are exposed. And, the researchers show, embryos that fail to form these memories remain a clump of clones, never realizing their unique biological potential.

Activating embryos

Over 25 years ago, Ali H. Brivanlou demonstrated that the protein Activin causes embryonic frog cells to take on traits specific to certain tissue types, a process called differentiation. For decades now, Activin has been thought to instigate the transition from homogenous clump to specialized cells.

"Activin was the textbook definition of a molecule that is necessary and sufficient for differentiation," says Brivanlou, the Robert and Harriet Heilbrunn Professor. "Researchers had shown that the dose of the protein determines cellular fate. At a very high dose, for example, you get gut and muscle; and at a very low dose, you get nerve tissue."

Despite ample evidence from animal studies, questions remained about how Activin guides development in human cells. Working with Brivanlou and Eric D. Siggia, the Viola Ward Brinning and Elbert Calhoun Brinning Professor, graduate fellow Anna Yoney set out investigate whether the protein triggers differentiation in laboratory-generated human embryos. Developed from stem cells, these embryos mimic the behavior of human cells during the early stages of development.

The researchers expected these synthetic embryos to respond just like Brivanlou's frogs. Yet, after applying Activin to these cells, they observed, well, nothing.

"Anna put Activin on the embryos and we waited--and waited and waited. And absolutely nothing happened! That was shocking," says Brivanlou.

Memorable molecules

Undeterred, Yoney considered possible explanations for her results. "I thought, Ok, we don't get a response from Activin alone," she recalls. "What additional signals might we need to see differentiation?"

She ultimately homed in on WNT, a molecule known to regulate the movement of cells during development. In her next experiment, she exposed the cells to WNT before adding Activin; and, this time, they differentiated in the normal manner.

"The cells that saw WNT reacted to Activin with the full range of response--just like we see in the frog and other animals," says Brivanlou. "But cells that hadn't seen WNT were totally unresponsive, as if Activin wasn't even there."

The researchers concluded that differentiation requires both WNT and Activin signaling. Crucially, however, they showed that cells needn't be exposed to the two chemicals simultaneously.

"We blocked WNT signaling during the Activin treatment phase and found that the cells still differentiated," says Yoney. "So we concluded that the cells actually remembered that they had previously been exposed to WNT."

The researchers deemed this phenomenon "signaling memory" because WNT appears to permanently change cells that cross its path. Earlier research in this area failed to uncover evidence for embryonic memories because, says Brivanlou, most developmental biologists work with animal cells.

"In animal model systems, cells encounter a series of signals before people like me manipulate them. But Anna's artificial embryos came from stem cells that hadn't had this kind of exposure--and this makes them perfect tools for discovering the roles of other signals," he says. "As beautiful as the model systems are, sometimes they can lead you to miss things."

The researchers hope to further explore how and where cellular memories are stored. Yoney suspects that they are recorded in cells' nuclei as modifications to the epigenome, which controls the way that cells read out their DNA. Additional research in this area could have major implications for understanding development in humans and other species.
-end-


Rockefeller University

Related Stem Cells Articles:

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.
First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
TSRI researchers identify gene responsible for mesenchymal stem cells' stem-ness'
Researchers at The Scripps Research Institute recently published a study in the journal Cell Death and Differentiation identifying factors crucial to mesenchymal stem cell differentiation, providing insight into how these cells should be studied for clinical purposes.
More Stem Cells News and Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.