A new study published in the journal Cell Stem Cell, describes how scientists have developed a way of producing highly sought populations of a pure tissue-specific cell from human pluripotent stem cells.
Human pluripotent stem cells (hPSCs) are precursor cells than can produce over 200 distinct cell types in the human body. They hold great promise for regenerative medicine and drug screening. The idea is to be able to generate a range of pure tissue types by manipulating these precursor cells.
However, it is proving very challenging to obtain large numbers of pure, untainted, tissue-specific cells from hPSCs. Part of the problem is how to ensure they receive highly specific signals, that do not coax them down paths that lead to a range of other tissue types.
Now, a team led by the Genome Institute of Singapore (GIS) in the Agency for Science, Technology and Research (A*STAR) has developed a new way of coaxing hPSCs to produce highly pure populations of endoderm, a valuable cell type that gives rise to organs like the liver and pancreas, bringing closer the day when stem cells can be used in clinical settings.
One of the study leaders is Dr. Bing Lim, senior group leader and associate director of Cancer Stem Cell Biology at the GIS. He and his colleagues developed a highly systematic and novel screening method.
The method teases out proteins and signaling chemicals that coax the formation of a single desired cell type, while at the same time blocking those that promote development of undesired cell types.
They found a combination of signals is involved in coaxing hPSCs to form pure populations of endoderm cells. Their work has effectively produced a “signaling roadmap” for the pathways involved.
The study also reveals new insights into how cell fates are decided during stem cell differentiation.
The authors write:
“We systematically blockaded alternate fates throughout multiple consecutive bifurcations, thereby efficiently differentiating multiple hPSC lines exclusively into endoderm and its derivatives.”
The team then used next-generation sequencing and bioinformatics to accurately identify key genetic elements that might guide cell differentiation.
They found dormant bits of DNA – known as enhancers, that become active and switch on neighboring genes when hPSCs differentiate – were already configured in the pre-differentiated cells.
In fact, they found a large superset of these “inactive enhancers,” all capable of converting to an active state on differentiation.
Thus the study provides not only a signaling roadmap, but also a comprehensive model of how enhancers regulate cell differentiation. This should be a very useful resource for stem cell researchers.
Thomas Graf, professor and coordinator of the Differentiation and Cancer Programme at the Center for Genomic Regulation, in Barcelona, Spain, comments on the study:
“Using this novel strategy, the work beautifully shows how hPSCs can be guided to differentiate into the endoderm cells at high efficiencies. The strategy described should be more widely applicable to other desired cell types.”
Dr. Lim adds:
“This unprecedented access to highly pure population of endodermal cells attracts pharmaceutical companies, who are interested in further making human liver cells to test drug toxicities.”
Meanwhile another group of researchers in Sweden reported success in developing a new way to increase supply of embryonic stem cells. They say their method could produce high-quality human embryonic stem cells on a large scale, without destroying embryos.