Earliest Step In Fetal Development Uncovered Through Unrelated Stem Cell Research

Posted Apr 11, 2008 by Nikki Weingartner
At Johns Hopkins University, researchers who had been focused on studying a rare blood disorder uncovered the genetic formation of the very beginning of human life: the placenta.
Findings that are to be published in the April issue of Cell Stem Cell have unveiled a model that will provide access to early human development that was not available before.
In a quote by Linzhao Chang, PhD, Associate Professor of Gynecology and Obstetrics and Co-Director of the Stem Cell Program at Johns Hopkins Institute for Cell Engineering
“This is one area of stem cell biology where human and mouse differ significantly and we never would have discovered this if we had limited our studies to using only mouse embryonic stem cells. Adult human stem cells just didn’t work for this.”
Through unrelated focused research studying a rare blood disorder caused by gene mutations, Linzhou’s team came across the gene that failed to form the trophoblast when BMP-4 was added, which later becomes the placenta in fetal growth and development.
A mutation on a certain gene known as PIG-A, the focal point of the team's research, could not be effectively studied due to a lack of appropriate models requiring them to remove the PIG-A gene. In mouse models, the unborn mice would either die before they were born or they did not reproduce symptoms found in patients with the blood disease.
Adult human stem cells did not work either, leading researchers to use human embryonic stem cells.
The embryonic stem cells provided successful in that researchers were able to replicate a study model and grow rare cells that lacked PIG-A, something they could not do before. However, their research proved a bit more beneficial to science than expected.
As part of the study, they needed to make sure that their “engineered” cells which were lacking in PIG-A would be able to develop into the normal fetal stages, starting with the trophoblast phase. Upon testing, they did not become trophoblasts.
Only when they added the PIG-A, [the gene that caused a blood disorder due to a mutation], back into their cells did BMP-4 do its work and cause the cells to become trophoblasts, allowing the researchers to conclude that trophoblast differentiation depends on certain cell surface proteins to receive the BMP-4 signal.
This finding is the basis for communication between a gene and BMP-4, signaling the beginning of placenta growth, or more importantly, the lifeline of a fetus. An amazing discovery that could have only been uncovered by this type of research.