Scientists Make Groundbreaking Discovery on Stem Cell Regulation

Source: Agency for Science, Technology and Research
Date: March 1, 2012

Summary:

A*STAR scientists have for the first time, identified that precise regulation of polyamine[1] levels is critical for embryonic stem cell (ESC) self-renewal – the ability of ESCs to divide indefinitely – and directed differentiation. This paper is crucial for better understanding of ESC regulation and was published in the journal Genes & Development on 1st March by the team of scientists from the Institute of Medical Biology (IMB), a research institute under the Agency for Science, Technology and Research (A*STAR).

Key to Aging? Key Molecular Switch for Telomere Extension by Telomerase Identified

Source: University of Illinois at Chicago
Date: November 23, 2011

Summary:

Researchers at the University of Illinois at Chicago College of Medicine describe for the first time a key target of DNA damage checkpoint enzymes that must be chemically modified to enable stable maintenance of chromosome ends by telomerase, an enzyme thought to play a key role in cancer and aging. Their findings are reported online in Nature Structural and Molecular Biology.

Important Step in Sperm Reprogramming Identified

Source: University of North Carolina School of Medicine
Date: September 22, 2011

Summary:

A study from the University of North Carolina at Chapel Hill School of Medicine has illuminated a key step of demethylation, giving stem cell researchers critical information as they try to reprogram adult cells to mimic the curative and self-renewing properties of stem cells. Previous research had shown that the methyl tags on sperm DNA are converted to their chemical cousin, hydroxymethyl, before disappearing completely. The current finding, published online in the Sept. 22, 2011, issue of Science (ScienceExpress), suggests that the disappearance of these chemical tags in the later steps of demethylation is not an active process catalyzed by an enzyme but is rather a passive process.

'Firefly' Stem Cells May Repair Damaged Hearts

Source: University of Central Florida
Date: September 28, 2010

Summary:

Stem cells that glow like fireflies could someday help doctors heal damaged hearts without cutting into patients' chests. In his University of Central Florida lab, Steven Ebert engineered stem cells with the same enzyme that makes fireflies glow. The "firefly" stem cells glow brighter and brighter as they develop into healthy heart muscle, allowing doctors to track whether and where the stem cells are working.

If doctors can figure out exactly how the cells repair and regenerate cardiac tissue, stem cell therapies could offer hope to more than 17.6 million Americans who suffer from coronary disease. The glow of the enzyme also means therapies would no longer require cutting into patients' chest cavities to monitor the healing. The study, funded by the National Institutes of Health and the American Heart Association, is a featured cover story in this month's highly ranked Stem Cells and Development Journal.

KEEPING STEM CELLS FROM CHANGING FATES

Source: Johns Hopkins Medicine
Date: September 8, 2010

Summary:

Johns Hopkins researchers have determined why certain stem cells are able to stay stem cells. The report in the June 4 issue of Cell Stem Cell reveals that an enzyme that changes the way DNA is packaged in cells allows specific genes to be turned on and off, thereby preventing a stem cell from becoming another cell type.

In breakthrough, nerve connections are regenerated after spinal cord injury

Source: University of California - Irvine
Date: August 8, 2010

Summary:

Researchers for the first time have induced robust regeneration of nerve connections that control voluntary movement after spinal cord injury, showing the potential for new therapeutic approaches to paralysis and other motor function impairments. In a study on rodents, the UC Irvine, UC San Diego and Harvard University team achieved this breakthrough by turning back the developmental clock in a molecular pathway critical for the growth of corticospinal tract nerve connections. They did this by deleting an enzyme called PTEN (a phosphatase and tensin homolog), which controls a molecular pathway called mTOR that is a key regulator of cell growth. PTEN activity is low early during development, allowing cell proliferation. PTEN then turns on when growth is completed, inhibiting mTOR and precluding any ability to regenerate. Results of the study appear online in Nature Neuroscience.

Gene essential to stem cell health discovered

Source: University of Hawaiʻi at Mānoa
Date: July 28, 2010

Summary:

Researchers at the University of Hawai‘i at Mānoa’s John A. Burns School of Medicine (JABSOM) have discovered a gene that is essential to keeping stem cells healthy. The gene, hypoxia inducible factor 1, helps keep levels of telomerase constant. Telomerase is an enzyme that is critical to a stem cell’s lifespan, helping to prevent or slow deterioration in the cells. When telomerase is reduced in a stem cell, the stem cell ages faster. The research results are published in July’s online edition of the Proceedings of the National Academy of Sciences (PNAS).

Researchers Create HIV-Resistant Cells

Source: University of Southern California
Date: July 6, 2010

Summary:

Researchers at the Keck School of Medicine of USC successfully have transplanted blood stem cells modified to be resistant to HIV into mice, allowing the animals to control HIV infections. If the approach can be translated to human patients, it would enable the long-term generation of HIV-resistant T cells in a patient’s body, and the potential for the patient’s own cells to suppress HIV. The strategy is explained in a new study published online in the journal Nature Biotechnology.

The approach targets a gene called CCR5, one of the two gateway molecules that HIV uses to enter human cells. Cannon’s strategy arose from the observation that people with a mutation in a gene called CCR5 are naturally resistant to infection with the most common strains of HIV and do not develop AIDS.

The team used enzymes called zinc finger nucleases — which physically cut DNA — to knock out the the CCR5 gene in human blood stem cells. The researchers transplanted these modified stem cells into mice, where they developed into mature cells of the human immune system, including the T cells that HIV infects. When the researchers then infected the animals with HIV, they found that the mice were able to maintain normal levels of the human T cells and suppress HIV to very low levels, unlike control mice that received unmodified stem cells.

Discovery of Cellular "Switch" May Provide New Means of Triggering Cell Death, Treating Human Diseases

Source: University of Colorado at Boulder
Date: March 11, 2010

Summary:

The discovery of a novel cellular “switch” in the popular laboratory research worm, C. elegans, by a University of Colorado at Boulder team may provide researchers with a new means of triggering programmed cell death in humans to treat disease.
A research team led by the University of Colorado at Boulder has discovered a previously unknown cellular "switch" that may provide researchers with a new means of triggering programmed cell death, findings with implications for treating cancer.

The new results are a big step forward in understanding programmed cell death, or apoptosis, a cell suicide process that involves a series of biochemical events leading to changes like cell body shrinkage, mitochondria destruction and chromosome fragmentation, said CU-Boulder Professor Ding Xue. But unlike traumatic cell death from injury, programmed cell death is a naturally occurring aspect of animal development that may help prevent human diseases like cancer and autoimmune disorders, said Xue, lead author on the new study.

Induced Pluripotent Stem Cells From Patients With a Premature Aging Disorder Bring Surprises

Source: Children's Hospital Boston
Date: February 17, 2010

Summary:

Boston, Mass. -- In a study that ties stem cell research together with research on aging and cancer, investigators at Children's Hospital Boston have used genetic reprogramming to create cells from patients with a rare premature-aging disorder that are able to rebuild their telomeres--the tips of chromosomes that must be maintained to prevent a cell from "aging" and enabling it to divide and make copies of itself.

Publishing in Nature (Advance Online) on February 17, researchers in the laboratory of George Q. Daley, MD, PhD, Director of the Stem Cell Transplantation Program at Children's, report successfully reactivating the cellular enzyme telomerase, which maintains the telomeres, in patients with dyskeratosis congenita. In this rare genetic disorder, genetic mutations cause telomerase to be defective, leaving the chromosomes without protection from damage and unable to compensate for the natural shortening of telomeres that occurs when a cell divides. As a result, a patient's cells "age" more quickly, leading to bone-marrow failure (an inability to make enough blood cells), degradation of multiple tissues, premature aging-like symptoms and a much-shortened lifespan.

USA Today and Technology Review carried news stories on this news release today.

Enzyme Necessary for Healthy Immune System, Study Finds

Source; University of California - Los Angeles
Date: January 6, 2010

Summary:

Mice without the deoxycytidine kinase (dCK) enzyme have defects in their adaptive immune system, producing very low levels of both T and B lymphocytes, the major players involved in immune response, according to a study by researchers with UCLA's Jonsson Comprehensive Cancer Center.

The finding could have ramifications in treating auto-immune disorders, in which the body attacks itself, and possibly certain cancers of the immune system. A drug could be developed to create lower levels of dCK in the body, thereby tamping down immune response. Such a drug might also be effective in transplant patients to decrease risk for rejection, said Dr. Caius Radu, an assistant professor of Molecular and Medical Pharmacology, a Jonsson Cancer Center researcher and senior author of the study.

The study, part of a long-term research project that has resulted in the development of a new probe for Positron Emission Tomography (PET) scanning and the creation of a non-invasive approach to observe chemotherapy at work in the body, appears this week in the early online edition of the Proceedings of the National Academy of Sciences.

Longevity tied to genes that preserve tips of chromosomes

Albert Einstein College of Medicine
November 11, 2009

Summary:

A team led by researchers at Albert Einstein College of Medicine of Yeshiva University has found a clear link between living to 100 and inheriting a hyperactive version of an enzyme that rebuilds telomeres – the tip ends of chromosomes. The findings appear in the latest issue of the Proceedings of the National Academy of Sciences.

In investigating the role of telomeres in aging, the Einstein researchers studied Ashkenazi Jews because they are a homogeneous population that was already well studied genetically. Three groups were enrolled: 86 very old — but generally healthy —
Gil Atzmon, Ph.D.people (average age 97); 175 of their offspring; and 93 controls (offspring of parents who had lived a normal lifespan).

Researchers found that participants who have lived to a very old age have inherited mutant genes that make their telomerase-making system extra active and able to maintain telomere length more effectively. For the most part, these people were spared age-related diseases such as cardiovascular disease and diabetes, which cause most deaths among elderly people.

Research May Hold Key to Maintaining Embryonic Stem Cells in Lab

Source: UT Southwestern Medical Center
Date: July 9, 2009

Summary:

In a new study that could transform embryonic stem cell (ES cell) research, scientists at UT Southwestern Medical Center have discovered why mouse ES cells can be easily grown in a laboratory while other mammalian ES cells are difficult, if not impossible, to maintain. If the findings in mice can be applied to other animals, scientists could have an entirely new palette of research tools to work with, said Dr. Steven McKnight, chairman of biochemistry at UT Southwestern and senior author of the study appearing in the July 9 issue of Science Express.

According to the research, the activation of a gene called TDH in mouse ES cells results in the cells entering a unique metabolic state that is similar to that of rapidly growing bacterial cells. The gene controls the production of the threonine dehydrogenase (TDH) enzyme in mouse ES cells. This enzyme breaks down an amino acid called threonine into two products. One of the two products goes on to control a cellular process called one carbon metabolism; the other provides ES cells with an essential metabolic fuel.

How an enzyme tells stem cells which way to divide

Source: University of Oregon
Date: May 14, 2009

Summary:

Driving Miranda, a protein in fruit flies crucial to switch a stem cell's fate, is not as complex as biologists thought, according to University of Oregon biochemists. They've found that one enzyme (aPKC) stands alone and acts as a traffic cop that directs which roads daughter cells will take.

"Wherever aPKC is at on a cell's cortex or membrane, Miranda isn't," says Kenneth E. Prehoda, a professor in the chemistry department and member of the University of Oregon's Institute of Molecular Biology. When a stem cell duplicates into daughter cells, the side, or cortical domain, containing aPKC (atypical protein kinase C) continues as a stem cell, while the other domain with Miranda becomes a differentiated cell such as a neuron that forms the central nervous system.

Prehoda and co-author Scott X. Atwood, who studied in Prehoda's lab and recently earned his doctorate, describe how the mechanism works in the May 12 issue of the journal Current Biology.

Scientists use 'biological alchemy' to convert one cell type into another

Source: Daily Telegraph - UK
Posted: 18 June 2008 6:01pm BST

Summary:

Scientists converted specialist "pancreatic exocrine cells" that secrete digestive enzymes, into beta cells, which make the hormone insulin to control blood sugar levels. This was achieved by locating genes that control how the genetic code is interpreted by cells to turn them into brain, bone, heart and other human cell types. The scientists discovered nine so called transcription factor genes were important for beta cell production. Using a standard method of genetic modification where a virus is used to introduced a gene, they injected the viruses into the pancreases of lab mice and found that some of the pancreatic exocrine cells turned into fully functional beta cells and produced insulin.

Enzyme plays key role in cell fate

Source: Baylor College of Medicine
Date: June 4, 2008

Summary:

The road to death or differentiation follows a similar course in embryonic stem cells, said researchers at Baylor College of Medicine in Houston in a report that appears online today in the journal Cell Stem Cell. Dr. Thomas Zwaka, assistant professor in the Stem Cells and Regenerative Medicine Center (STaR) at BCM, and his colleagues at BCM found an “overlap between the pathways that drive cell death and cell differentiation” in a group of enzymes called caspases.

Researchers Determine Structure of Protein Involved in Spastic Paraplegia

Source: Howard Hughes Medical Institute
Date; January 17, 2008

Summary:

By piecing together the detailed structure of a molecule-munching enzyme, researchers from the Howard Hughes Medical Institute (HHMI) have revealed how it helps maintains cells' internal highways. The finding could one day lead to new treatments for a neurological disorder caused when the enzyme, known as spastin, malfunctions.

Regulating Embryonic Stem Cell Self-Renewal

Source: Cold Spring Harbor Laboratory
Date: October 15, 2007

Summary:

Researchers have identified two genes – called Jmjd1a and Jmjd2c – that regulate self-renewal in embryonic stem cells. This finding will have important ramifications for embryonic stem cell research.

Enzyme Eliminated by Cancer Cells Holds Promise for Cancer Treatment

Source: Medical College of Georgia
Date: July 18, 2007

Summary:

An enzyme that cancer cells eliminate, apparently so they can keep proliferating, may hold clues to more targeted, effective cancer treatment, scientists say.

Shaggy-haired mice aid cell-aging research

Source: San Francisco Chronicle
Date: August 18, 2005

Summary:

Stanford University biologists have created a strain of long-haired laboratory mice that suggest a surprising new role for an enzyme already linked to aging and cancer.