Biological complexity: white blood cells from stem cells (Introduction)

by David Turell , Monday, May 20, 2019, 17:54 (2014 days ago) @ David Turell

A complex ballet of protein molecules:

https://phys.org/news/2019-05-zebrafish-explore-alternatives-bone-marrow.html

"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, Ph.D., 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."

Comment: This complex development system requires three specific proteins to work in combination and finally add a phosphate group to Fzd9b's tail to set off production by a stem cell. This has to be designed from the beginning. Chance attempts won't work to put this series of reactions in place.