Posted on 05/19/2008 9:00:06 PM PDT by neverdem
While it has long been known that embryonic stem cells have the ability to develop into any kind of tissue-specific cells, the exact mechanism as to how this occurs has heretofore not been demonstrated. Now, researchers at the Hebrew University of Jerusalem and elsewhere have succeeded in graphically revealing this process, resolving a long-standing question as to whether the stem cells achieve their development through selective activation or selective repression of genes.
The collaborative research group, which included Dr. Eran Meshorer of the Department of Genetics at the Silberman Institute of Life Sciences at the Hebrew University of Jerusalem, has revealed that the embryonic stem (ES) cells express large proportions of their genome "promiscuously." This permissive expression includes lineage-specific and tissue-specific genes, non-coding regions of the genome that are normally "silent," and repetitive sequences in the genome, which comprise the majority of the mammalian genome but are also normally not expressed.
When ES cells differentiate into specific cell tissue-types, they undergo global genetic silencing. But until this occurs, the ES cells maintain an open and active genome. This might very well be the secret of their success, since by maintaining this flexibility they maintain their capacity to become any cell type. Once silencing, or genetic repression, occurs, this ability is gone.
Thus, one can say that the ES cells stand at the ready until the "last minute" -- prepared to engage in selective activation into specific cells -- holding "in abeyance" their ability to become any kind of cells at the point and time required.
To reveal the process as to how this occurs, the researchers created the first full-mouse genomic platform of DNA microarrays. Microarrays are glass-based chips that allow simultaneous detection of thousands of genes. The microarrays used in the study were not confined to specific genes only but spanned the entire genome.
Hundreds of such microarrays were required in the study to cover the entire genome in different time points during stem cell differentiation. It was by observation of these sequences that the researchers were able to establish exactly how and at what point the stem cells developed into specific tissue cells and when the silencing occurs.
---------------------------- Article adapted by Medical News Today from original press release. ----------------------------
The project carried out by the researchers appears in the latest issue of the journal Cell Stem Cell. The collaborators in addition to Dr. Meshorer who participated in the project include Tom Misteli, Ron McKay, Stuart Le Grice, Sol Efroni and Kenneth Buetow of the US National Institutes of Health, Thomas Gingeras of Affymetrix Inc. of Santa Clara, Calif., and David Bazett-Jones of The Hospital for Sick Children, Toronto.
Source: Jerry Barach The Hebrew University of Jerusalem
The molecular mechanisms underlying pluripotency and lineage specification from embryonic stem cells (ESCs) are largely unclear. Differentiation pathways may be determined by the targeted activation of lineage-specific genes or by selective silencing of genome regions. Here we show that the ESC genome is transcriptionally globally hyperactive and undergoes large-scale silencing as cells differentiate. Normally silent repeat regions are active in ESCs, and tissue-specific genes are sporadically expressed at low levels. Whole-genome tiling arrays demonstrate widespread transcription in coding and noncoding regions in ESCs, whereas the transcriptional landscape becomes more discrete as differentiation proceeds. The transcriptional hyperactivity in ESCs is accompanied by disproportionate expression of chromatin-remodeling genes and the general transcription machinery. We propose that global transcription is a hallmark of pluripotent ESCs, contributing to their plasticity, and that lineage specification is driven by reduction of the transcribed portion of the genome.
stem cell ping
This is an incredibly important advance, if it is borne out by further research... possibly the most important of this year.
This is an incredibly important advance, if it is borne out by further research... possibly the most important of this year.
A good follow-up to the development of the ability to convert adult skin cells to embryonic ones. That presumably will be the really big one - tho how does a scientist win the Nobel Prize for research that proves that liberals are wrong about the need for research on the cells of incipient unique babies?
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