Protein required to maintain full potential of stem cells

Researchers at the University of California, San Francisco have pinpointed a protein that is critical for maintaining a stem cell’s full potential to self-renew and to differentiate. Stem cells lacking the protein were impaired in their ability to divide and make identical copies of themselves, called self-renewal. These cells also lost their capacity to differentiate into key cell types, such as cardiac muscle. The protein, Chd1, acts to keep chromosome strands loosely wound, which permits widespread gene activation in the cell’s nucleus. Previous studies hypothesized that this open chromosome structure is necessary in stem cells to maintain their potential to specialize into any cell type. Additional results in this study demonstrate that Chd1 is required for efficient reprogramming of adult cells, such as skin cells, back into a pluripotent state. These new insights into Chd1 function may lead to safer, more efficient methods for growing up large numbers of embryonic stem cells and deriving specific cell types, both critical steps for successful stem cell therapeutic strategies.

Nature, July 8, 2009 (online publication)
CIRM funding: Rupa Sridharan (T1-00002), Kathrin Plath (RN1-00564-1), Miguel Ramalho-Santos (RS1-00434-1)

Related Information: press release, University of California, San Francisco

Genetic differences found between adult cell and embryonic-derived stem cells

Researchers at the University of California, Los Angeles have found genetic differences that distinguish induced pluripotent stem (iPS) cells from embryonic stem cells. These differences diminish over time, but never disappear entirely. iPS cells are created when adult cells, such as those from the skin, are reprogrammed to look and behave like embryonic stem cells. But until now, scientists didn’t know if the two types of stem cells were actually identical at a molecular level. This latest research shows that iPS and embryonic stem cells differ in which genes they have turned on or off. All early iPS cells share these genetic traits, regardless of what animal they come from, the type of adult cells the iPS cells start as, or what method was used to reprogram those adult cells. However, later cultures of iPS cells show that most, but not all, of these differences disappear over time, making later cultures of iPS cells more similar to embryonic stem cells. If scientists want to use iPS cells in medical therapies, this research will give them a better idea of how similar they are to embryonic stem cells.

Cell Stem Cell: July 2, 2009
CIRM funding: Mike Teitell (RS1-00313), Kathrin Plath (RN1-00564-1), William Lowry (RS1-00259-1, RL1-00681-1)

Related Information: Press Release, University of California, Los Angeles

Genetic Brake Key to Stem Cell Fate

Researchers at UC, Santa Barbara, have mapped the role of a genetic signal that puts the breaks on the ability of stem cells to self renew. The finding could eventually shed light on self-renewal that has run amuck as in cancer, and can immediately be put to use in managing the balancing act between self-renewal and differentiation—the process through which stem cells mature into more specific cell types such as neurons or muscle.  Specifically, they found that a microRNA, a single-stranded RNA whose function is to decrease gene expression, lowers the activity of three key genes needed for embryonic stem cell self-renewal. Conversely, they found that when this microRNA, miR-145, is lost the stem cells are prevented from differentiating into more mature cells.

Cell: April 30, 2009
CIRM funding: Na Xu (T3-00009)

Related Information: Press release, University of California, Santa Barbara

Protein Flips Switch In Embryonic Stem Cell Growth

Researchers at the Burnham Institute for Medical Research and the Scripps Research Institute have found that a protein known to play an important role in maintaining mouse embryonic stem cells has a similarly crucial job in human embryonic stem cells. This protein, called Shp2, acts as a switch, telling the cells to either divide to make more of themselves – a process called self-renewal – or to mature into different cell types – called differentiation. Fine-tuning this balance between self-renewal and differentiation will be critical for developing new therapies based on embryonic stem cells. The cells need to self-renew in order to grow up enough cells to be therapeutically useful. Once researchers have sufficient cells, they need to switch the cells over to a state where they can mature into cell types such as nerves, retinal cells, or pancreatic islets that can be used to study or treat disease.

PLoS ONE: March 17, 2009
CIRM funding: Yuhong Pang (T2-00004)

Related Information: Press Release, Burnham Institute for Medical Research

Origin of blood stem cells found to be in the lining of blood vessels

Researchers at UC, Los Angeles have found that blood-forming stem cells in mice have their origins in the endothelial cells that line blood vessels during mid-gestation. These cells eventually move to the bone marrow where they generate all the cells of the blood system throughout life. Researchers have long known that blood-forming stem cells arise from the blood vessels, but didn’t know exactly which cell type acted as the source. Now that the source is know, the researchers want to learn what signals those endothelial cells to begin producing blood-forming stem cells. This information could eventually help researchers learn how to create those stem cells in the lab and maintain the cells in the stem cell state rather than forming mature cell types. Currently, it isn’t possible to grow blood stem cells in large quantity in the lab. Having a source of these cells would be useful for bone marrow transplants to treat cancer or for research purposes.

Cell Stem Cell: December 4, 2008
CIRM funding: Ann Zovein (T1-00005)

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

Genetic Factors Found to Speed Embryonic Stem Cell Division

Researchers at UC, San Francisco developed a novel way of finding out the role of DNA-relatives called microRNA. These molecules are known to turn genes on and off and appear to regulate whether embryonic stem cells remain as stem cells or develop into mature cell types, but learning which genes are controlled by each microRNA has been a challenge. Using this screen, the researchers found 14 microRNAs that speed up cell division; of those, five are commonly found in human embryonic stem cells. It turns out these microRNAs deactivate genes that slow the cell cycle, essentially releasing the brakes on cell division. Identifying the role of these and other microRNAs could help researchers understand how to hold embryonic stem cells in their immature state, guide how those cells mature, or even develop treatments for cancer.

Nature Genetics: November 2, 2008
CIRM funding: Yangming Wang (T1-00002)

Related Information: Press release, UCSF Institute for Regeneration Medicine, Blelloch bio

Genetic Profile Distinguishes Types of Stem Cells

Researchers at the The Scripps Research Institute found a new way of classifying the many cell types that fall under the category of “stem cells.” The term stem cell refers to tissue specific stem cells found in mature tissues such as blood, brain, or muscle, which are restricted to forming only cells found in those tissues, as well as to embryonic stem cells that are broadly able to form all cells of the body. The term is also used to refer to the so-called induced pluripotent stem (iPS) cells that scientists can now create out of adult skin cell and that mimic embryonic stem cells in their ability to form a variety of cell types. In this work, the researchers discovered a set of genes that are always active in the pluripotent cells – whether they were iPS cells or embryonic stem cells. As more stem cell populations become available, the gene profile discovered in this study will help researchers distinguish those cells that are truly pluripotent from those that are more restricted in the cell types they are able to form.

Nature: September 18, 2008
CIRM funding: Louise Laurent (T1-00003)

Related Information: Scripps news story, The Scripps Research Institute

Human Embryonic Stem Cells Trigger Immune Reaction in Mice

Researchers at the Stanford University School of Medicine have found that human embryonic stem cells trigger an immune response much like organ rejection when transplanted into mice. In the past, researchers had thought that transplanted embryonic stem cells might not be rejected the way transplanted organs are. Testing this theory, the team found that after transplanting human embryonic stem cells into normal mice, those cells disappeared within seven to ten days. In mice without an immune system the cells survived and even multiplied. Drugs used to prevent organ rejection also successfully prevented normal mice from rejecting the transplanted stem cells. These results suggest that any therapy involving transplanted embryonic stem cells will also require a way of preventing people from rejecting those therapeutic cells.

Proceedings of the National Academy of Sciences: September 2, 2008
CIRM funding: Joseph Wu (RS1-00322)

Related Information: Press Release, Stanford Stem Cell Biology and Regenerative Medicine Institute, Wu bio

Fly Stem Cells Create their Home

Researchers at the Salk Institute of Biological Studies discovered that stem cells in the testes of fruit flies are able to generate their own support cells. This work in flies could help guide researchers hoping to understand the environment surrounding resident populations of human stem cells - called the niche. The niche is difficult to study in humans but is an area of great interest because any therapy based on transplanting stem cells into a tissue will require those cells to be paced in a niche where they will thrive. This work raises the possibility that some transplanted stem cells may be able to produce their own niche.

Nature: July 20, 2008
CIRM funding: Justin Voog (T1-00003)

Related Information: Salk press release, Salk Institute for Biological Studies

Pattern of Small Genetic Factors Found to Characterize Embryonic Stem Cells

Researchers at The Scripps Research Institute discovered that human embryonic stem cells have a very specific signature when it comes to the regulators of their genes. MicroRNAs are very small, naturally occurring bits of genetic material. They don't code for specific proteins like genes do, but they regulate the activity of genes and turn on and off their protein production. In embryonic stem cells microRNAs are actively preventing the production of proteins that tell cells to differentiate into specific heart or bone tissue, for example, but are pushing hard on genes that result in self-renewal. The team hopes to use these microRNAs to reprogram any type of cell to become as pluripotent as embryonic stem cells and to do it more safely than current reprogramming called iPS.

Stem Cells: June, 2008
CIRM funding: Louise Laurent (T1-00003)

Related Information: Press release , The Scripps Research Institute

Genes Found that Characterize Embryonic Stem Cells

Researchers at UC, San Francisco identified a group of genes that are active in embryonic stem cells but not in more differentiated cells. They also developed a technique to find DNA regions that could be important for activating these genes, and identified a factor that directs the production of proteins from genes that contain these regulatory DNA regions. These studies will greatly inform research efforts that rely on maintaining a stem cell's ability to proliferate and to generate the many different cell types in a human body.

PLoS Genetics: August 2007
CIRM funding: Marcia Grskovic (T1-00002)

Related Information: UCSF Institute for Regeneration Medicine

Key Protein Involved in Forming Nuclear Membrane after Division Found

Researchers at UC, San Diego found the function of a key protein involved in the cell cycle, the process by which a cell duplicates all its genes and divides. The protein is critical to the assembly of the membrane around the cell's nucleus. A fundamental understanding of the cell cycle is integral to advancing all cell-based therapies.

Proceedings of the National Academy of Sciences: April 17, 2007
CIRM funding: Youngjun Kim (T1-00003)

Related Information: UCSD Stem Cell Initiative