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Phosphorylation of Sox2 Cooperates in Reprogramming to Pluripotent Stem Cells

From the December Issue of Stem Cells

By Stuart P Atkinson

Modifications of histone proteins have been well studied in ESCs and iPSCs and we are beginning to understand the importance that these modifications have in relation to chromatin structure and gene regulation and indeed the enzymes which mediate these modifications. However, research into modifications of non-histone proteins in pluripotent cells has perhaps lagged behind. Studies in 2009 Saxe et al, Swaney et al and Van Hoof et al) have provided an excellent insight into the global picture of protein phosphorylation in ECs and ESCs, which included the modification of both OCT4 and SOX2, and recently Nanog has been shown to be regulated by phosphorylation Moretto-Zita et al). Now, in the December issue of Stem Cells, the lab of Zigang Dong from The Hormel Institute at the University of Minnesota provides data from an in depth analysis of the specific role of Sox2 phosphorylation in mouse ESC Jeong et al), supporting a potential role in pluripotency and reprogramming.

Phosphorylation of Sox2 Cooperates in Reprogramming to Pluripotent Stem Cells

From the December Issue of Stem Cells

By Stuart P Atkinson

Modifications of histone proteins have been well studied in ESCs and iPSCs and we are beginning to understand the importance that these modifications have in relation to chromatin structure and gene regulation and indeed the enzymes which mediate these modifications. However, research into modifications of non-histone proteins in pluripotent cells has perhaps lagged behind. Studies in 2009 Saxe et al, Swaney et al and Van Hoof et al) have provided an excellent insight into the global picture of protein phosphorylation in ECs and ESCs, which included the modification of both OCT4 and SOX2, and recently Nanog has been shown to be regulated by phosphorylation Moretto-Zita et al). Now, in the December issue of Stem Cells, the lab of Zigang Dong from The Hormel Institute at the University of Minnesota provides data from an in depth analysis of the specific role of Sox2 phosphorylation in mouse ESC Jeong et al), supporting a potential role in pluripotency and reprogramming.

Reprogramming Somatic Cells – Down to One Gene!

From Cell Stem Cell

A new study from the lab of Sheng Ding (The Scripps Research Institute), published recently in Cell Stem Cell, reports the reprogramming of human primary somatic cells using only OCT4 gene transduction and a combination of small molecules. Kim et alhad previously shown than one factor reprogramming is possible, but in human foetal neural stem cells, a cell source perhaps not readily available. iPSCs were generated at an efficiency of roughly 1 colony in 250,000 target cells over an 8 week period utilising neonatal human epidermal keratinocytes (NHEKs). The group also went on to generate iPSCs from human umbilical vein endothelial cells (HUVECs) and amniotic fluid-derived cells (AFDCs). Through a screening process, a novel small molecule activator of 3-phosphoinositide-dependent kinase-1 (PDK1), PS48, was also discovered to be useful in the reprogramming process. It was hypothesised that this small molecule may facilitate a metabolic conversion from mitochondrial oxidation to glycolysis during the reprogramming process, or in other words, metabolically reprogram the cells. The authors note that “differential use of glycolytic metabolism over mitochondrial oxidation by pluripotent cells would favour pluripotency by promoting proliferation/cell cycle transitions with less oxidative stress.”

Reprogramming Somatic Cells – Down to One Gene!

From Cell Stem Cell

A new study from the lab of Sheng Ding (The Scripps Research Institute), published recently in Cell Stem Cell, reports the reprogramming of human primary somatic cells using only OCT4 gene transduction and a combination of small molecules. Kim et alhad previously shown than one factor reprogramming is possible, but in human foetal neural stem cells, a cell source perhaps not readily available. iPSCs were generated at an efficiency of roughly 1 colony in 250,000 target cells over an 8 week period utilising neonatal human epidermal keratinocytes (NHEKs). The group also went on to generate iPSCs from human umbilical vein endothelial cells (HUVECs) and amniotic fluid-derived cells (AFDCs). Through a screening process, a novel small molecule activator of 3-phosphoinositide-dependent kinase-1 (PDK1), PS48, was also discovered to be useful in the reprogramming process. It was hypothesised that this small molecule may facilitate a metabolic conversion from mitochondrial oxidation to glycolysis during the reprogramming process, or in other words, metabolically reprogram the cells. The authors note that “differential use of glycolytic metabolism over mitochondrial oxidation by pluripotent cells would favour pluripotency by promoting proliferation/cell cycle transitions with less oxidative stress.”

New Study into Bladder Regeneration Heralds Organ Replacement Treatment

Durham, NC (November 2010) - Researchers in the United States have developed a medical model for regenerating bladders using stem cells harvested from a patient’s own bone marrow. The research, published in STEM CELLS, is especially relevant for paediatric patients suffering from abnormally developed bladders, but also represents another step towards new organ replacement therapies.

The research, led by Drs. Arun Sharma and Earl Cheng from the Feinberg School of Medicine at Northwestern University, focused on bone marrow mesenchymal stem cells (MSCs) taken from the patient. Previously studies into the regenerative capacity of cells in bladders have focused on animal models, but these have translated poorly in clinical settings.

Stem-cell pioneer says clear law is needed

By Marie McCullough
Inquirer Staff Writer

Is it legal for the federal government to fund human embryonic stem cell research?

Next month, a federal appeals court will hear arguments, yea and nay. Any decision is sure to be appealed because current laws are ambiguous.
And that's the problem, said John Gearhart, head of the University of Pennsylvania's Institute for Regenerative Medicine - and one of the first two scientists to isolate human embryonic stem cells in 1998.

Stem-cell pioneer says clear law is needed

By Marie McCullough
Inquirer Staff Writer

Is it legal for the federal government to fund human embryonic stem cell research?

Next month, a federal appeals court will hear arguments, yea and nay. Any decision is sure to be appealed because current laws are ambiguous.
And that's the problem, said John Gearhart, head of the University of Pennsylvania's Institute for Regenerative Medicine - and one of the first two scientists to isolate human embryonic stem cells in 1998.

iPSCs Provide HIV “Killer” Cells

by Stuart P. Atkinson

From the lab of Dan Kaufman at the Department of Medicine and Stem Cell Institute, University of Minnesota comes a report on the potential use of patient specific human induced pluripotent stem cells (hiPSCs) in the battle against HIV-1 infection. Kaufman’s lab have previously shown that embryonic stem cell (ESC) derived Natural Killer (NK) cells, a key component of the innate immune system, can potentially kill tumour cells in vivo and dramatically reduce tumour size in vitro Woll et aland Woll et al). Several studies have also shown that NK cells can provide protection against HIV-1 replication in which sufferers show decreased NK cell function. In their most recent study published in the Journal of Virology, Kaufman’s lab now demonstrate that NK cells derived from human ESC (hESC) and also hiPSCs have potent anti-HIV-1 activity Ni et al).

iPSCs Provide HIV “Killer” Cells

by Stuart P. Atkinson

From the lab of Dan Kaufman at the Department of Medicine and Stem Cell Institute, University of Minnesota comes a report on the potential use of patient specific human induced pluripotent stem cells (hiPSCs) in the battle against HIV-1 infection. Kaufman’s lab have previously shown that embryonic stem cell (ESC) derived Natural Killer (NK) cells, a key component of the innate immune system, can potentially kill tumour cells in vivo and dramatically reduce tumour size in vitro Woll et aland Woll et al). Several studies have also shown that NK cells can provide protection against HIV-1 replication in which sufferers show decreased NK cell function. In their most recent study published in the Journal of Virology, Kaufman’s lab now demonstrate that NK cells derived from human ESC (hESC) and also hiPSCs have potent anti-HIV-1 activity Ni et al).

“linc”ing Non-Coding RNAs with Pluripotency and Reprogramming

By Stuart P. Atkinson

Little by little, the processes behind cellular reprogramming of lineage-committed cells to induced pluripotent stem cells (iPSCs) are being discovered and more detailed comparative studies between iPSC and embryonic stem cells (ESCs) are being undertaken. The similarity of these two cell types is generally viewed as being essential if hiPSCs are to be taken towards the clinic and while this has led to detailed analyses of many cellular attributes, such as mRNA expression, miRNA expression and chromatin structure, other “avenues” remain relatively unstudied.

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