Category Archives: Stem Cells

Newswise New research findings show that embryonic stem cells unable to fully compact the DNA inside them cannot complete their primary task: differentiation into specific cell types that give rise to the various types of tissues and structures in the body.

Researchers from the Georgia Institute of Technology and Emory University found that chromatin compaction is required for proper embryonic stem cell differentiation to occur. Chromatin, which is composed of histone proteins and DNA, packages DNA into a smaller volume so that it fits inside a cell.

A study published on May 10, 2012 in the journal PLoS Genetics found that embryonic stem cells lacking several histone H1 subtypes and exhibiting reduced chromatin compaction suffered from impaired differentiation under multiple scenarios and demonstrated inefficiency in silencing genes that must be suppressed to induce differentiation.

While researchers have observed that embryonic stem cells exhibit a relaxed, open chromatin structure and differentiated cells exhibit a compact chromatin structure, our study is the first to show that this compaction is not a mere consequence of the differentiation process but is instead a necessity for differentiation to proceed normally, said Yuhong Fan, an assistant professor in the Georgia Tech School of Biology.

Fan and Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, led the study with assistance from Georgia Tech graduate students Yunzhe Zhang and Kaixiang Cao, research technician Marissa Cooke, and postdoctoral fellow Shiraj Panjwani.

The work was supported by the National Institutes of Healths National Institute of General Medical Sciences (NIGMS), the National Science Foundation, a Georgia Cancer Coalition Distinguished Scholar Award, and a Johnson & Johnson/Georgia Tech Healthcare Innovation Award.

To investigate the impact of linker histones and chromatin folding on stem cell differentiation, the researchers used embryonic stem cells that lacked three subtypes of linker histone H1 -- H1c, H1d and H1e -- which is the structural protein that facilitates the folding of chromatin into a higher-order structure. They found that the expression levels of these H1 subtypes increased during embryonic stem cell differentiation, and embryonic stem cells lacking these H1s resisted spontaneous differentiation for a prolonged time, showed impairment during embryoid body differentiation and were unsuccessful in forming a high-quality network of neural cells.

This study has uncovered a new, regulatory function for histone H1, a protein known mostly for its role as a structural component of chromosomes, said Anthony Carter, who oversees epigenetics grants at NIGMS. By showing that H1 plays a part in controlling genes that direct embryonic stem cell differentiation, the study expands our understanding of H1s function and offers valuable new insights into the cellular processes that induce stem cells to change into specific cell types.

During spontaneous differentiation, the majority of the H1 triple-knockout embryonic stem cells studied by the researchers retained a tightly packed colony structure typical of undifferentiated cells and expressed high levels of Oct4 for a prolonged time. Oct4 is a pluripotency gene that maintains an embryonic stem cells ability to self-renew and must be suppressed to induce differentiation.

H1 depletion impaired the suppression of the Oct4 and Nanog pluripotency genes, suggesting a novel mechanistic link by which H1 and chromatin compaction may mediate pluripotent stem cell differentiation by contributing to the epigenetic silencing of pluripotency genes, explained Fan. While a significant reduction in H1 levels does not interfere with embryonic stem cell self-renewal, it appears to impair differentiation.

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Successful Stem Cell Differentiation Requires DNA Compaction

ScienceDaily (May 11, 2012) New research findings show that embryonic stem cells unable to fully compact the DNA inside them cannot complete their primary task: differentiation into specific cell types that give rise to the various types of tissues and structures in the body.

Researchers from the Georgia Institute of Technology and Emory University found that chromatin compaction is required for proper embryonic stem cell differentiation to occur. Chromatin, which is composed of histone proteins and DNA, packages DNA into a smaller volume so that it fits inside a cell.

A study published on May 10, 2012 in the journal PLoS Genetics found that embryonic stem cells lacking several histone H1 subtypes and exhibiting reduced chromatin compaction suffered from impaired differentiation under multiple scenarios and demonstrated inefficiency in silencing genes that must be suppressed to induce differentiation.

"While researchers have observed that embryonic stem cells exhibit a relaxed, open chromatin structure and differentiated cells exhibit a compact chromatin structure, our study is the first to show that this compaction is not a mere consequence of the differentiation process but is instead a necessity for differentiation to proceed normally," said Yuhong Fan, an assistant professor in the Georgia Tech School of Biology.

Fan and Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, led the study with assistance from Georgia Tech graduate students Yunzhe Zhang and Kaixiang Cao, research technician Marissa Cooke, and postdoctoral fellow Shiraj Panjwani.

The work was supported by the National Institutes of Health's National Institute of General Medical Sciences (NIGMS), the National Science Foundation, a Georgia Cancer Coalition Distinguished Scholar Award, and a Johnson & Johnson/Georgia Tech Healthcare Innovation Award.

To investigate the impact of linker histones and chromatin folding on stem cell differentiation, the researchers used embryonic stem cells that lacked three subtypes of linker histone H1 -- H1c, H1d and H1e -- which is the structural protein that facilitates the folding of chromatin into a higher-order structure. They found that the expression levels of these H1 subtypes increased during embryonic stem cell differentiation, and embryonic stem cells lacking these H1s resisted spontaneous differentiation for a prolonged time, showed impairment during embryoid body differentiation and were unsuccessful in forming a high-quality network of neural cells.

"This study has uncovered a new, regulatory function for histone H1, a protein known mostly for its role as a structural component of chromosomes," said Anthony Carter, who oversees epigenetics grants at NIGMS. "By showing that H1 plays a part in controlling genes that direct embryonic stem cell differentiation, the study expands our understanding of H1's function and offers valuable new insights into the cellular processes that induce stem cells to change into specific cell types."

During spontaneous differentiation, the majority of the H1 triple-knockout embryonic stem cells studied by the researchers retained a tightly packed colony structure typical of undifferentiated cells and expressed high levels of Oct4 for a prolonged time. Oct4 is a pluripotency gene that maintains an embryonic stem cell's ability to self-renew and must be suppressed to induce differentiation.

"H1 depletion impaired the suppression of the Oct4 and Nanog pluripotency genes, suggesting a novel mechanistic link by which H1 and chromatin compaction may mediate pluripotent stem cell differentiation by contributing to the epigenetic silencing of pluripotency genes," explained Fan. "While a significant reduction in H1 levels does not interfere with embryonic stem cell self-renewal, it appears to impair differentiation."

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Successful stem cell differentiation requires DNA compaction, study finds

ALBANY -- Almost halfway through a $600 million state program supporting stem cell research, eight medical schools around New York are reporting progress on projects such as replicating liver cells and eradicating leukemia cells.

A new report from Associated Medical Schools of New York updates work at the institutions where hundreds of researchers are starting to unravel causes and potential treatments for conditions ranging from autism to heart disease and cancer. Stem cells are self-renewing and have the ability to develop into other types of cells.

The Mount Sinai School of Medicine reported finding a method to transform human skin cells into stem cells and turned differentiated human stem cells into heart cells. Those findings are expected to result in better understanding of how heart disease develops and allow initial testing of new treatments on stem cells before they are used on human subjects.

Dr. Ihor Lemischka, director of the Black Family Stem Cell Institute at Mount Sinai, said recreating heart cells in a dish from a patient with LEOPARD Syndrome, a disease caused by a genetic mutation, has opened ongoing avenues for researching the disease and screening potential drugs.

"It was a major achievement," Lemischka said. The initial work was reported in June 2010 in the journal Nature.

The shared research facility at Mount Sinai supports the work at 80 different labs, Lemischka said.

The Empire State Stem Cell Program was intended to fund projects in early stages, including those that initially have been unable to get federal or private funding. Grants have also been used for capital projects like renovating labs and establishing new stem cell centers.

The Albert Einstein College of Medicine reported replicating liver cells that could help reduce the need for liver transplants using live donors and cadavers.

Dr. Allan Spiegel said 12 new researchers have been hired with state funding at the Bronx school, which also lists anemia, brain disorders, heart disease and obesity among its stem cell research subjects.

"It offers tremendous potential for understanding the causes of and developing better treatments for diseases like cancer, type 1 diabetes and Parkinson's," he said.

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New York medical schools chart progress with stem cells

ALBANY, N.Y. (AP) Almost halfway through a $600 million state program supporting stem cell research, eight medical schools around New York are reporting progress on projects such as replicating liver cells and eradicating leukemia cells.

A new report from Associated Medical Schools of New York updates work at the institutions where hundreds of researchers are starting to unravel causes and potential treatments for conditions ranging from autism to heart disease and cancer. Stem cells are self-renewing and have the ability to develop into other types of cells.

The Mount Sinai School of Medicine reported finding a method to transform human skin cells into stem cells and turned differentiated human stem cells into heart cells. Those findings are expected to result in better understanding of how heart disease develops and allow initial testing of new treatments on stem cells before they are used on human subjects.

Dr. Ihor Lemischka, director of the Black Family Stem Cell Institute at Mount Sinai, said recreating heart cells in a dish from a patient with LEOPARD Syndrome, a disease caused by a genetic mutation, has opened ongoing avenues for researching the disease and screening potential drugs.

"It was a major achievement," Lemischka said. The initial work was reported in June 2010 in the journal Nature.

The shared research facility at Mount Sinai supports the work at 80 different labs, Lemischka said.

The Empire State Stem Cell Program was intended to fund projects in early stages, including those that initially have been unable to get federal or private funding. Grants have also been used for capital projects like renovating labs and establishing new stem cell centers.

The Albert Einstein College of Medicine reported replicating liver cells that could help reduce the need for liver transplants using live donors and cadavers.

Dr. Allan Spiegel said 12 new researchers have been hired with state funding at the Bronx school, which also lists anemia, brain disorders, heart disease and obesity among its stem cell research subjects.

"It offers tremendous potential for understanding the causes of and developing better treatments for diseases like cancer, type 1 diabetes and Parkinson's," he said.

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NY medical schools chart progress with stem cells

Source: ISNA, Tehran

Iranian researcher and lecturer Radbod Darabi jointly with his collogues from the University of Minnesota's Lillehei Heart Institute have effectively treated muscular dystrophy in mice using human stem cells derived from a new process which for the first time makes the production of human muscle cells from stem cells efficient and effective.

Radbod Darabi, MD, PhD with Rita Perlingeiro, PhD. (Credit: Image courtesy of University of Minnesota Academic Health Center)

The research outlines the strategy for the development of a rapidly dividing population of muscle-forming cells derived from induced pluripotent (iPS) cells.

IPS cells have all of the potential of embryonic stem (ES) cells, but are derived by reprogramming skin cells. They can be patient-specific, which renders them unlikely to be rejected, and do not involve the destruction of embryos.

This is the first time that human stem cells have been shown to be effective in the treatment of muscular dystrophy.

According to the researchers, there has been a significant lag in translating studies using mouse stem cells into therapeutically relevant studies involving human stem cells.

This lag has dramatically limited the development of cell therapies or clinical trials for human patients.

The latest research from the University of Minnesota provides the proof-of-principle for treating muscular dystrophy with human iPS cells, setting the stage for future human clinical trials.

As the researchers noted one of the biggest barriers to the development of cell-based therapies for neuromuscular disorders like muscular dystrophy has been obtaining sufficient muscle progenitor cells to produce a therapeutically effective response.

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Iranian researcher helps treating muscular dystrophy using stem cells