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A Nucleolar Link to Pluripotency and Reprogramming?

By Stuart P. Atkinson

Delineation of the mechanisms by which embryonic stem cells (ESC) remain pluripotent and maintain the ability to differentiate across all germ lineages has attracted many studies which altogether can be consolidated into an information network which combines transcription factors, chromatin and DNA modifications, small RNAs and signal transduction pathways. Analyses of the interactions within this network will unravel the mechanisms underlying these properties into something we can begin to understand and appreciate. Such analysis may also lend itself to the discovery of new ways to produce safer and better induced pluripotent stem cells (iPSC) reprogrammed from somatic cells. In order to uncover new mechanisms underlying pluripotency and lineage specification, researchers from the laboratory of Sheng Ding have taken a new approach, using individually-arrayed cDNA libraries representing more than 30,000 clones, for the identification of new genes which affect pluripotency. This new study is published online in Stem Cells.

A Nucleolar Link to Pluripotency and Reprogramming?

By Stuart P. Atkinson

Delineation of the mechanisms by which embryonic stem cells (ESC) remain pluripotent and maintain the ability to differentiate across all germ lineages has attracted many studies which altogether can be consolidated into an information network which combines transcription factors, chromatin and DNA modifications, small RNAs and signal transduction pathways. Analyses of the interactions within this network will unravel the mechanisms underlying these properties into something we can begin to understand and appreciate. Such analysis may also lend itself to the discovery of new ways to produce safer and better induced pluripotent stem cells (iPSC) reprogrammed from somatic cells. In order to uncover new mechanisms underlying pluripotency and lineage specification, researchers from the laboratory of Sheng Ding have taken a new approach, using individually-arrayed cDNA libraries representing more than 30,000 clones, for the identification of new genes which affect pluripotency. This new study is published online in Stem Cells.

hES say G1-yeS!

By Stuart P. Atkinson

The potential applications of human embryonic stem cells (hESC) in regenerative medicine are far reaching, but the need for large numbers of these cells requires prolonged in vitro culture which can lead to the accumulation of unwanted genetic changes and potentially, tumorigenicity.

hES say G1-yeS!

By Stuart P. Atkinson

The potential applications of human embryonic stem cells (hESC) in regenerative medicine are far reaching, but the need for large numbers of these cells requires prolonged in vitro culture which can lead to the accumulation of unwanted genetic changes and potentially, tumorigenicity.

US give Geron Go-ahead for ESC Trial for Spinal Cord Injury

Widely reported

The US Food and Drug Administration (FDA) has authorised Geron to carry out the world's first clinical trial using human embryonic stem cells (hESC) in patients with acute spinal cord injury. GRNOPC1 contains hESC-derived oligodendrocyte progenitor cells that have been shown to have the ability to restore function in animal models of acute spinal cord injury (Keirstead et al.). The Phase I clinical trial won initial approval in January last year but was delayed due to safety concerns raised in animal studies in which a higher frequency of small cysts was observed within the injury site in the spinal cord of animals injected than in other studies. However, further studies in rats addressed these safety concerns and Geron now plans to test the therapy on around 10 volunteer patients paralysed by spinal cord injuries. The initial phase will be testing for safety and Geron has selected up to seven U.S. medical centres as candidates to participate in this study and in planned protocol extensions.

Sources

Daily Telegraph (UK)

Financial Times (UK)

Medical News Today

Associated Press

Keirstead, H.S., G. Nistor, G. Bernal, M. Totoiu, F. Cloutier, K. Sharp, and O. Steward, Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci, 2005. 25(19): p. 4694-705.

US give Geron Go-ahead for ESC Trial for Spinal Cord Injury

Widely reported

The US Food and Drug Administration (FDA) has authorised Geron to carry out the world's first clinical trial using human embryonic stem cells (hESC) in patients with acute spinal cord injury. GRNOPC1 contains hESC-derived oligodendrocyte progenitor cells that have been shown to have the ability to restore function in animal models of acute spinal cord injury (Keirstead et al.). The Phase I clinical trial won initial approval in January last year but was delayed due to safety concerns raised in animal studies in which a higher frequency of small cysts was observed within the injury site in the spinal cord of animals injected than in other studies. However, further studies in rats addressed these safety concerns and Geron now plans to test the therapy on around 10 volunteer patients paralysed by spinal cord injuries. The initial phase will be testing for safety and Geron has selected up to seven U.S. medical centres as candidates to participate in this study and in planned protocol extensions.

Sources

Daily Telegraph (UK)

Financial Times (UK)

Medical News Today

Associated Press

Keirstead, H.S., G. Nistor, G. Bernal, M. Totoiu, F. Cloutier, K. Sharp, and O. Steward, Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci, 2005. 25(19): p. 4694-705.

It´s better to stick together – overexpressing E-cadherin helps iPSC generation

by Lyle Armstrong

One of the hallmarks of any of the techniques currently used to generate induced pluripotent stem cells (iPSCs) is low efficiency although continual efforts are being made to enhance the numbers of reprogrammed cell colonies obtained from a given number of somatic cells. Added to this are the data originating from research groups whose aim is to reprogram the somatic genome to pluripotency without resort to viral vectors by using small molecule treatments to increase the expression levels of key pluripotency associated genes such as OCT4 to the point where their roles in epigenetic reprogramming become apparent.

iPSC’s “Memory” Suggests Limited Use Compared to ESC

Two advance articles in Nature and Nature Biotechnology from the labs of Konrad Hochedlinger, George Daley and Andrew Feinberg have suggested that iPSC retain a “memory” of their initial state, and therefore may be of limited use in regenerative medicine. When studying murine iPSC, it was found that the epigenetic profile of the mouse donor cell wasn’t entirely “erased” and the differentiation potential of the iPSC was linked to the cell of origin. Further analysis of this type in human iPSC may decide whether iPSC technology as we know it will be a suitable replacement for hESC derivation.

Also see the following news items from BusinessWeek, Nature and The-Scientist.

iPSC’s “Memory” Suggests Limited Use Compared to ESC

Two advance articles in Nature and Nature Biotechnology from the labs of Konrad Hochedlinger, George Daley and Andrew Feinberg have suggested that iPSC retain a “memory” of their initial state, and therefore may be of limited use in regenerative medicine. When studying murine iPSC, it was found that the epigenetic profile of the mouse donor cell wasn’t entirely “erased” and the differentiation potential of the iPSC was linked to the cell of origin. Further analysis of this type in human iPSC may decide whether iPSC technology as we know it will be a suitable replacement for hESC derivation.

Also see the following news items from BusinessWeek, Nature and The-Scientist.

An Interview with Patricia Labosky

patricialabosky


By Carla B. Mellough

Featured Lab Article

Patricia Labosky,

‘In college I had a couple of professors that I would just love to listen to in lectures. It became clear to me that these essential questions in cell and developmental biology were important to me, and the way I wanted to focus my career.´

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