“Latest Stem Cells News”

While only a small portion of autism spectrum disorders (ASDs) can be traced to their genetic roots, those that can are most often part of Fragile X syndrome (FXS), the most commonly known single-gene cause of autism. FXS is associated with the loss of the FMR protein (FMRP) coded by the mental retardation gene 1, FMR1 gene.

While scientists understand the biochemical nuances of these mutations, their implications on neuronal development and function remain a mystery. To address this puzzle, HSCI Associate Faculty member Stephen Haggarty, PhD, reprogrammed a series of both mutated and non-mutated cells back into a stem cell state in which they have the ability to derive new tissues.

Haggarty and his team found that the FMR1 mutations present in the induced pluripotent stem cells (iPSCs) do not always resemble those in the naturally occurring cells from which they came. This offers valuable information as other researchers begin to design investigations using these iPSCs.

Additionally, the team used the cell lines to generate a variety of neuronal cell types. While FMRP loss did not prevent neurodevelopment, it did impact cell quality, suggesting an important role for FMRP early in human neurodevelopment. These findings will allow researchers to characterize existing drugs and develop new therapies for the treatment of some ASDs.

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Tweaking the levels of factors used during the reprogramming of adult cells into induced pluriopotent stem (iPS) cells greatly affects the quality of the resulting iPS cells, according to Whitehead Institute researchers.

“This conclusion is something that I think is very surprising or unexpected—that the levels of these reprogramming factors determine the quality of the iPS cells,” says Whitehead Founding Member Rudolf Jaenisch. “We never thought they’d make a difference, but they do.”

An article describing this work is published in the December 2 issue of Cell Stem Cell.

“This conclusion is something that I think is very surprising or unexpected—that the levels of these reprogramming factors determine the quality of the iPS cells,” says Whitehead Founding Member Rudolf Jaenisch. “We never thought they’d make a difference, but they do.”

iPS cells are made by introducing specific reprogramming genes into adult cells. These factors push the cells into a pluripotent state similar to that of embryonic stem (ES) cells. Like ES cells, iPS cells can become any cell type in the body, a characteristic that could make them well-suited for therapeutic cell transplantation or for creating cell lines to study such diseases as Parkinson’s and Alzheimer’s.

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By irradiating typical polystyrene lab plates with ultraviolet (UV) waves, Whitehead Institute and MIT scientists have created a surface capable of tripling the number of human embryonic stem (ES) and induced pluripotent stem (iPS) cells that can be grown in culture by current methods. Use of this novel surface also eliminates the need for layers of mouse “feeder cells” to support ES- and iPS-cell growth.

“Polystyrene is the most common cell culture surface used in labs, and to be able to do a simple treatment and get something that works better than the mouse feeder layers is great and potentially has a lot of utility,” says Daniel Anderson, Associate Professor in the Harvard-MIT Division of Health Sciences & Technology.

The research is published online this week in the Proceedings of the National Academy of Sciences (PNAS).

“I think it’s going to be a useful technique,” says Krishanu Saha, a postdoctoral researcher in Whitehead Member Rudolf Jaenisch’s lab. “There is a lot of push, at least in the field, to [eliminate animal products]. If you were one day to inject these cells into patients, you wouldn’t have to worry about as many safety risks as if you had co-cultured them with animal cells.”

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Announcer: Recently, Dr. Ricardo Dolmetsch, an associate professor of neurobiology at Stanford, spoke with National Institute of Mental Health Director Dr. Thomas Insel. Devoted to Autism Spectrum Disorder research, Dr. Dolmetsch and his colleagues have generated stem cells from children with autism allowing them to study how the brain develops in children with ASD.

Dr. Thomas Insel: I thought a good place to begin the conversation was to ask you about your interest in autism and how that happened. You’re someone who trained in calcium channels… worked on very basic problems in molecular biology and now you’re interested in autism…

Dr. Ricardo Dolmetsch: Right, when I first got to Stanford I was interested in a very basic question.. and um.. you know for a few years we worked on that and that was really exciting but it was very arcane. And then about I guess four and a half years ago, our son was diagnosed with autism. And so this really changed my…the direction of my lab. Actually, what really happened was that my wife and I got together and we thought a little bit about what we could do and we came up with a bunch of projects and one of the ideas was that we were going to just change all of our efforts and that’s how we started working on autism.

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The same genes that are chemically altered during normal cell differentiation, as well as when normal cells become cancer cells, are also changed in stem cells that scientists derive from adult cells, according to new research from Johns Hopkins and Harvard.

Although genetically identical to the mature body cells from which they are derived, induced pluripotent stem cells (iPSCs) are notably special in their ability to self-renew and differentiate into all kinds of cells. And now scientists have detected a remarkable if subtle molecular disparity between the two: They have distinct “epigenetic” signatures; that is, they differ in what gets copied when the cell divides, even though these differences aren’t part of the DNA sequence.

“Relatively little study has been done on the epigenetic nature of stem cells,” says Andrew Feinberg, M.D., M.P.H., a professor of medicine at the Johns Hopkins University School of Medicine. “To date, the bulk of what is known about stem cells is focused on how you create them and grow them and so forth, but not on the essence of them, and what is fundamentally different about these cells.”

To compare and contrast mature connective tissue cells called fibroblasts with the pluripotent stem cells into which they were reprogrammed, the investigators focused on a chemical change known as methylation. This chemical change which, associated with silencing genes, is classified as epigenetic because, although not part of the DNA sequence, is copied when a cell divides. They identified and then measured so-called differentially methylated regions (DMRs) of genes whose expression was changed in the process of being reprogrammed from a parent cell to a stem cell.

Building on previous research that looked at where differently methylated sites were located in cancer cells, as well as on research that had shown these same sites matching up with many of the methylated areas that had been implicated in the differentiation of normal brain, liver and spleen tissues, the team discovered that the reprogramming of a cell to become a stem cell apparently involves many of the very same DMRs and genes.

“The surprise,” says Feinberg, “is that there is such a degree of overlap between the differently methylated regions and genes that are involved in turning a fibroblast into a stem cell and turning a normal cell into a cancer cell.”

The study, done jointly with George Q. Daley, M.D., Ph.D., and colleagues from Harvard University, was published Nov. 1 in the advanced online edition of Nature Genetics. The researchers suggest in the study that certain sites throughout the genome appear to be generally involved in distinguishing DNA methylation among different cell types and cancers, and these same sites are involved in reprogramming fibroblasts back into stem cells (…)

from http://newswire.ascribe.org/cgi-bin/behold.pl?ascribeid=20091104.074444&time=09%2059%20PST&year=2009&public=0

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Researchers and using stem cells as tools for disease study, drug screening, clinical trial strategy, and personalized medicine. The induced Pluripotent Stem cell (iPS) is giving us a chance to rethink the way we are developing new drugs. These iPS cells are usually created from somatic cells (such as skin), and not embryos or adult stem cells. In creating iPS from patients’ diseased cells, scientists can study the disease in vitro, looking for disease phenotypes, applying microenvironmental stress, and testing new drugs. Compared to animal model testing (e.g. mice), this represents a significant breakthrough, that can be used to validate clinical development strategy and test efficacy in specific groups of patients. iPS is bringing a revolution in drug discovery methodology which is being used to bridge genetics, cell biology, and physiology.

from http://biobusiness.tv/videos/208

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