Protein found to direct embryonic stem cells as they mature

Researchers at the Stanford University School of Medicine have found that clusters of embryonic stem cells in a lab dish share some unexpected similarities with actual embryos. These clumps, called embryoid bodies, consist of hundreds of cells, many of which begin to form more mature cell types. For example, they often contain groups of primitive heart muscle cells that beat visibly. In this work the researchers found that the embryoid bodies also contain a line of cells that resemble an embryonic structure called the primitive streak. This streak is the first indication that the embryo has a top and bottom or back and front. Blocking molecules found in the embryoid body primitive streak pushed those cells to form a group of cells that make up skin and nerves. Enhancing those molecules pushed the cells to form cell types like muscle and intestine. This work could help researchers learn how to push embryonic stem cells to form particular cell types, which is a necessary step in developing stem cell-based therapies.

Cell Stem Cell: November 6, 2008
CIRM funding: Roel Nusse (RC1-00133-1)

Related Information: Press release, Stanford Stem Cell Biology and Regenerative  Medicine Institute, Nusse lab page

Early immune cells created from embryonic stem cells

Researchers at UC, Los Angeles have created cells that go on to form normal T cells out of human embryonic stem cells. What’s more, these cells were grown in the absence of animal feeder cells, which are usually needed to sustain embryonic stem cells. Avoiding potential contamination by such feeder cells is an important step in generating cells that can be transplanted into people. The researchers describe a series of steps that drive human embryonic stem cells to begin developing as T cells. When they transplanted the cells into mice with human thymus tissue, where T cells normally mature, those cells did mature into normal adult T cells. In addition, the group inserted genes into their immature T cells before transplantation and saw evidence that those genes were active in the mature, transplanted cells. This work brings researchers closer to creating cells that can be transplanted into people as a therapy for disorders of the immune system, including HIV/AIDS.

Stem Cells: October 30, 2008 (online publcation)
CIRM funding: Zoran Galic (RS1-00203), Aparna Subramaniana (T1-00005), Jerome Zack (RC1-00149)

Related Information: The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA , Zack bio

Method Produces Nerve Cells More Quickly

Researchers at the Burnham Institute for Medical Research have developed a new way of quickly maturing embryonic stem cells into neural cells. Other research groups have worked out lab conditions that encourage embryonic stem cells to mature into various types of nerve cells, but those methods were slow and resulted in early stage nerve cells that were more likely to cause tumors when transplanted into mice. This new method could speed work by researchers who are trying to develop therapies for diseases of the nervous system. As an additional benefit, this work showed that some previously overlooked genes are worth studying as potential regulators of embryonic stem cell maturation.

Cell Death and Differentiation: March 13, 2009
CIRM authors: R Bajpai (T2-00004), Stuart Lipton (RC1-00125), Alexi Terskikh (RS1-00466)

Related Information: Press release, Burnham Institute for Medical Research, Lipton bio, Terskikh bio

Genetic Factors Found to Regulate Embryonic Stem Cell Maturation

Researchers at UC, San Francisco identified a molecule that regulates differentiation of embryonic stem cells. In some cases, small molecules of the genetic material RNA have the ability to turn genes on and off rather than carrying out the normal RNA function of coding for proteins. These small RNAs, called micro RNA or miRNA, are thought to be one way the cell regulates genes that control how stem cells differentiate into mature cell types. In this study, the researchers created genetically altered mouse embryonic stem cells that lack the miRNA DGCR8. These cells did not respond properly to signals that would normally cause stem cells to differentiate into mature cell types. Even after the cells began differentiating they continued making proteins that are normally only found in embryonic stem cells. This work shows that miRNAs are key molecules to target for controlling ES cell differentiation, which is essential for developing safe protocols for stem cell-based therapies.

Nature Genetics: March, 2007
CIRM funding: Yanging Wang (T1-00002)

Related Information: UCSF Institute for Regeneration Medicine