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

Molecules found that control the development of blood vessel cells

Researchers at the Gladstone Institute of Cardiovascular Disease have identified two molecules, called microRNAs, that push early heart cells to mature into the smooth muscle cells that line blood vessels. These same molecules also control when those smooth muscle cells divide to repair damage or in diseases such as cancer or atherosclerosis, which both involve unhealthy blood vessel growth. The two microRNAs, miR-145 and miR-143, are abundant in the primitive heart cells of prenatal mice, leading those cells to differentiate into various mature heart and aorta cells. After birth, both microRNAs are present mainly in smooth muscle cells, which also line the small intestine. If both microRNAs are absent, smooth muscle cells in blood vessels start multiplying. This helps heal injured blood vessels, but it can also create abnormal blood vessel growth in certain diseases. This cell proliferation can thicken blood vessels in atherosclerosis, or it can nourish tumors with blood. These findings could help scientists create smooth muscle cells from embryonic stem cells for therapeutic uses, or could lead to therapies for atherosclerosis or cancer.

Nature, July 5, 2009 (online publication)
CIRM funding: Deepak Srivastava (RC1-00142-1), Kathy Ivey (T2-00003)

Related Information: Press Release, Gladstone Institute of Cardiovascular Disease, Srivastava bio

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

Embryonic stem cells repair nerve damage from mutiple sclerosis in mice

Researchers at the University of California, Irvine have found that neurons derived from  embryonic stem cells were able to repair some damage in a mouse model of multiple sclerosis. In people with MS, the immune system attacks the insulation – called myelin – that covers and protects neurons of the brain and spinal cord. The transplanted cells caused a response in the animals that allowed the myelin coating to be repaired on damaged cells. In humans, repairing the myelin would likely also repair the function of those nerves, bringing back feeling and motor control in people with MS. At this time there are no therapies to repair this damage. Instead, available drugs simply slow the progression of the disease. In this early study, the transplanted neurons survived only two weeks. The authors say more work is needed to understand how the remyelination occurred and how to retain the transplanted cells.

Journal of Neuroimmunology: May 23, 2009 (online)
CIRM funding: Chris Shaumberg (T1-00008), Thomas Lane (RS1-0409)

Related Information: University of California, Irvine

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

Genetic molecule enables safer method for creating iPS cells

Researchers at the University of California, San Francisco have designed a safer technique for reprogramming adult cells into a state that resembles embryonic stem cells. This method takes advantage of genetic molecules called microRNAs, which regulate the activity of genes. The original 2007 method for creating reprogrammed cells, called induced pluripotent stem (iPS) cells, relied on inserting four genes, some potentially tumor-causing, into the DNA of an adult cell such as a skin cell. Since then, researchers have whittled the number of genes down to two, and in one case generated iPS cells with only chemicals. However, the process is often inefficient. In this study, the researchers substituted one of the four genes with a microRNA molecule and obtained iPS cells at high efficiency. The researchers suggest microRNAs could replace other genes or improve the efficiency of chemical means of creating iPS cells. In addition, understanding how microRNAs function in reprogramming could lead to new therapeutic strategies for blocking reprogramming in cancer stem cells.



Nature Biotechnology, April 12, 2009
CIRM funding: Robert Blelloch (RS1-00161)

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

Protein protects brain from damage, may prevent neurodegenerative diseases

Researchers at the University of California, San Diego and the Salk Institute for Biological Studies have found a protein that protects the brain from the kind of damage that can lead to Parkinson's disease. This protein, called Nurr1, has a long history in Parkinson's disease research. People who carry a mutation in the gene are prone to developing the disease. The new work explains how the protein prevents Parkinson's disease and could also help researchers find ways of treating of preventing the disease. The protein was especially important in two types of cells that protect and support the brain's neurons -- called microglia and astrocytes. In these cells, Nurr1 works with other proteins to limit inflammation after an immune response. Without it, these support cells produced toxic by-products that damaged the nerves in a way that could lead to Parkinson's disease or other neurodegenerative diseases.

Cell: April 3, 2009
CIRM funding: Beate Winner and Fred H. Gage (RC1-00115), Christian Carson (T3-00007), Leah Boyer (T1-00003)

Related Information: Press release, University of California, San Diego, Salk Institute for Biological Studies, Gage bio