Scientists make pure precursor liver and pancreas cells from stem cells

Date: Jan-29-2014A 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.

Team develops signaling roadmap for coaxing hPSCs into pure endoderm cells

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."

Team also produces model of 'inactive enhancers'

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.

Written by Catharine Paddock PhD




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