Nav: Home

Zebrafish help researchers explore alternatives to bone marrow donation

May 20, 2019

Blood diseases such as leukemia and lymphoma are currently treated with bone marrow transplants -- a transfer of blood stem cells from a healthy person to a patient in need. But the demand for patient-matched blood stem cells far exceeds their availability, and many patients go without. To bypass the need for donations, University of California San Diego School of Medicine researchers are using zebrafish and human cells to determine how to grow blood stem cells in a laboratory dish.

Whether it's humans or zebrafish, a major player driving embryonic and blood cell development is the Wnt family of molecules. These molecules tell cells what to do by docking on Frizzled receptors, which sit on cell surfaces like antennae.

In their latest study, published May 20, 2019 by Nature Cell Biology, the team was surprised to discover that when one particular Wnt signaling molecule, Wnt9a, is received by blood stem cells, three different molecules are involved. Scientist had previously thought there were only two.

That third -- and, it turns out, crucial -- factor is the epidermal growth factor receptor, or EGFR. This finding may help advance the development of blood stem cells in the laboratory.

"Previous attempts to develop blood stem cells in a laboratory dish have failed, and that may be in part because they didn't take the interaction between EGFR and Wnt into account," said first author Stephanie Grainger, PhD, assistant project scientist at UC San Diego School of Medicine.

Researchers commonly use zebrafish -- a pet shop staple -- to study how blood stem cells develop in a normal organism. Zebrafish are an ideal model for this because they use the same mechanisms to make blood stem cells that humans do, but they are translucent as they develop. That means researchers can watch their blood stem cells arise in real time, and test how genetic modifications affect them.

According to the study, blood stem cell development works like this: The Wnt9a molecule touches down on a Frizzled receptor on the outer surface of a blood stem cell (Fzd9b, to be exact). At the same time, Wnt9a also brings EGFR into the mix from the outside of the cell, bringing Fzd9b and EGFR closer together. Then, inside the cell, EGFR tags Fzd9b's inner tail with a chemical, a phosphate group. This last step triggers a cascade of cellular events necessary to turn a stem cell into a blood cell.

The researchers said identifying EGFR in this context was also exciting because many cancer therapies work by targeting this receptor.

"Our findings raise the possibility that such treatments will impact Wnt signaling," said Karl Willert, PhD, associate professor at UC San Diego School of Medicine and faculty member in the Sanford Consortium for Regenerative Medicine. "We currently don't know how EGFR inhibitors will impact the biology of blood stem cells, and future studies will certainly have to take these interactions into account." Willert was co-senior author of the study with David Traver, PhD, professor at UC San Diego School of Medicine and Division of Biological Sciences.

Now that the team has determined how blood stem cells receive this Wnt signal at the cell surface, they will focus on unraveling how the cells relay and process the signal. Then they can start thinking about ways to trick the cells into thinking they have received this cue, even if they have not. That technique would better enable researchers to generate human blood stem cells in the laboratory -- and perhaps one day use off-the-shelf blood stem cells, instead of bone marrow transplants, to treat patients with blood diseases.

Cancer cells often hijack these same developmental pathways to grow and form tumors. Grainger said learning how cells communicate with each other through Wnt, Frizzled and EGFR might provide a new approach to treating malignancies where these signals are out of control.

"This is a great example of how working in one area of biology can have a huge impact on a seemingly unrelated process," said Willert, who is also director of the Human Embryonic Stem Cell Core Facility at UC San Diego School of Medicine. "In this case, we were studying Wnt's role in blood development and we landed smack in the middle of the EGFR-cancer field."
-end-
Co-authors of the study include: Nicole Nguyen, Jenna Richter, Jordan Setayesh, Brianna Lonquich, Chet Huan Oon, Jacob M. Wozniak, Rocio Barahona, Jack Houston, Marvic Carrillo-Terrazas, David Gonzalez, UC San Diego; Caramai N. Kamei, Massachusetts General Hospital; and Iain A. Drummond, Massachusetts General Hospital and Harvard Medical School.

University of California - San Diego

Related Stem Cell Articles:

Oncotarget Characterization of iPS87, a prostate cancer stem cell-like cell line
Oncotarget Volume 11, Issue 12 reported outside its natural niche, the cultured prostate cancer stem cells lost their tumor-inducing capability and stem cell marker expression after approximately 8 transfers at a 1:3 split ratio.
Stem cell identity unmasked by single cell sequencing technology
Scientists from The University of Queensland's Diamantina Institute have revealed the difference between a stem cell and other blood vessel cells using gene-sequencing technology.
It's all about the (stem cell) neighborhood
Researchers at Duke-NUS Medical School have now identified how the stem cell neighbourhood, known as a niche, keeps stem cells in the gut alive.
Spaceflight activates cell changes with implications for stem cell-based heart repair
A new study of the effects of spaceflight on the development of heart cells identified changes in calcium signaling that could be used to develop stem cell-based therapies for cardiac repair.
Not just a stem cell marker
The protein CD34 is predominantly regarded as a marker of blood-forming stem cells but it helps with migration to the bone marrow too.
Interferon-beta producing stem cell-derived immune cell therapy on liver cancer
Induced pluripotent stem (iPS) cell-derived myeloid cells (iPS-ML) that produce the anti-tumor protein interferon-beta (IFN-beta) have been produced and analyzed by researchers from Kumamoto University, Japan.
Scientists aim to create the world's largest sickle cell disease stem cell library
Scientists at the Center for Regenerative Medicine at Boston Medical Center and Boston University School of Medicine are creating an induced pluripotent stem cell (iPSC)-based research library that opens the door to invaluable sickle cell disease research and novel therapy development.
Designer switches of cell fate could streamline stem cell biology
Researchers at the University of Wisconsin-Madison have developed a novel strategy to reprogram cells from one type to another in a more efficient and less biased manner than previous methods.
Allen Institute for cell science releases gene edited human stem cell lines
The Allen Institute for Cell Science has released the Allen Cell Collection: the first publicly available collection of gene edited, fluorescently tagged human induced pluripotent stem cells that target key cellular structures with unprecedented clarity.
Feng Zhang receives 2016 New York Stem Cell Foundation -- Robertson Stem Cell Prize
The New York Stem Cell Foundation (NYSCF) announced today that Feng Zhang, Ph.D., is the 2016 recipient of the NYSCF -- Robertson Stem Cell Prize for his pioneering advances to edit human and plant genomes using CRISPR-Cas9.
More Stem Cell News and Stem Cell 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

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.