Complexity of Embryonic Stem Cells.
Genes Linked to the Growth and Differentiation of hESCs.
Monday, 17 May 2004
Geron Corporation today present research results that identify genes active in human embryonic stem cells (hESCs) and in hESCs undergoing differentiation. The work was performed under Geron's prior collaboration with Celera Genomics Group, and was published online today in the journal Nature Biotechnology (doi:10.1038/nbt971).
This work has elucidated signalling pathways operative in hESCs that likely play key roles in their growth and differentiation. This information will facilitate derivation of useful differentiated cell types for therapy, and may also lead to the development of novel tools for drug discovery.
Geron and Celera produced cDNA libraries from undifferentiated hESCs and three partially differentiated progeny cell populations. cDNA libraries were constructed from undifferentiated hES cells (uhES), embryoid body (EB) outgrowth, hepatocyte-like cells (preHep) and neuroectoderm-like cells (preNeu) derived from the same passage uhES cells. 50,000 clones per library were subjected to 5' EST sequencing. The 148,453 ESTs obtained were reduced in size into 32,764 distinct assemblies, by sequence similarity to one another and to UniGene public database, representing expressed genes in the human genome. All 148,000 sequences are available from the National Center for Biotechnology Information.
Examination of these ESTs revealed 532 significantly upregulated and 140 significantly downregulated genes in the undifferentiated hESCs. These data highlight changes in the transcriptional network that occur when hES cells differentiate. Among the differentially regulated genes are several components of signalling pathways and transcriptional regulators that likely play key roles in hESC growth and differentiation.
The authors state that these genomic data may facilitate the derivation of clinically useful cell types from hESCs.
"This work represents a unique large scale comparison of genes expressed in undifferentiated hESCs and their differentiated progeny," said Ralph Brandenberger, Ph.D., Geron's group leader of bioinformatics and lead author on the paper.
"This approach allows fine discrimination of gene expression patterns between directly related cell types permitting identification of genes likely to be important in the maintenance of undifferentiated hESCs and in the transition to the early differentiated state. The data also show differences between mouse and human embryonic stem cells and the different mechanisms each uses to maintain the undifferentiated 'pluripotent' state."
"Controlling the growth and differentiation of hESCs is key to developing well characterised cell populations for therapeutic use," stated Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer.
"The information provided by this study has resulted in new inventions which may help us achieve this," Okarma further said.
This extensive expression analysis of hESCs and early differentiated cell lines obtained from them show how complex the issue is about the therapeutic usefulness of ES cells. It should be obvious for anyone involved that a lot more hESC lines are needed for successful research and ultimate use of stem cells for curing and healing the many diseases they hold promise for.
Unfortunately this seems still not be the case for the top administrators in the Bush government, as last weeks letter from the NIH director Dr. Elias Zerhouni reiterated. In answering members of the House of Representatives in their calling for the President to reconsider his stem cell policy, Zerhouni wrote:
"Today, much of the basic research that needs to be done can be and is being supported with federal funds under the president's policy."
"And although it is fair to say that from a purely scientific perspective more cell lines may well speed some areas of human embryonic stem cell research, the president's position is still predicated on his belief that taxpayer funds should not 'sanction or encourage further destruction of human embryos that have at least the potential for life."
The letter to members of Congress clearly shows that the White House does not plan to back off the policy limiting federal funding of embryonic stem cell research any time soon.
The present policy has already left US research on hESC three years behind the rest of the world; more seriously it will still for a long time prolong the suffering of millions of people that could be treated with the new stem cell therapies. All possible resources should be made available for this kind of promising research.
Even though much work and money are invested in hESC research worldwide already, the contribution from the US is vital for the rapid success and development of therapeutic valid treatments. Therefore it is of worldwide interest that the present restrictive US policy on the use of human eggs, early embryo’s and hESCs is reversed as soon as possible. Will it take the American people to choose a different President to again endorse medical progress instead of hindering the research?
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References and links:
Publication of Genetic Data Describing Genes Linked to the Growth and Differentiation of Human Embryonic Stem Cells
Press Release Monday May 17, 2004
Source: Geron Corporation
Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation
Nature Biotechnology
16 May, 2004 doi:10.1038/nbt971
NIH Chief Reiterates Stem Cell Policy – Washington Post, 05/15/2004
Government Signals No Change on Stem Cells – Reuters, 05/15/2004
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L.
Ed.
CellNEWS
04-05-17
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