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Production of Mouse Embryonic Stem Cell Lines from Maturing Oocytes by Direct Conversion of Meiosis into Mitosis

From the March 2011 Issue of Stem Cells

Paper Commentary by Stuart P. Atkinson

Induced pluripotent stem cells (iPSC) have the potential to provide a patient specific source of cells that can be used in cellular therapy. However doubts about their similarity to embryonic stem cells (ESCs) have arisen, both at the gene expression and epigenetic level, and also with their initial differentiation capabilities and the capacity of the differentiated cells to function properly. So what other potential sources do we have? Currently derived human ESC lines (hESC) may not have the genetic diversity required, whilst derivation of additional hESC lines has associated ethical (and funding) problems. Meanwhile, hESC-derivation from somatic cell nuclear transfer (SCNT) has yet to yield results and does not look likely to in the short term. For many, iPSCs still represent the future of stem cell research and stem cell derivation. However, another source of pluripotent cells which are often overlooked may be available, in the form of parthenogenetic stem cells. Parthenogenetic ESCs are derived from activated oocytes at the metaphase II stage and could provide a patient specific source of ESCs for the donor female, and perhaps relatives of the said donor (Hikichi et al. and Kim et al.). However donated oocytes at this stage of development are generally used in assisted reproduction and are therefore of scarce availability, a problem also associated with SCNT. However, Josef Fulka Jr’s group at the Institute of Animal Science, Pratelstvi, Prague have now demonstrated a new method of creating parthenogenetic ESCs from metaphase I oocytes, which are often discarded during the course of IVF, by using Butyrolactone I (BL1). This study (Fulka et al.) is presented in the March Edition of Stem Cells.

Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Mitochondrial function is understood to play a key role in the ageing process and mitochondrial dysfunction underlies the pathophysiology of various diseases. Whilst much attention has focused on the role of the genetic and epigenetic state on cell function and differentiation in stem cells, little work thus far has addressed the contribution of cell metabolism in stem cell function and activity. New results reported in the March edition of Stem Cells by Mandal et al. from the University of California and Indian Institute of Science Education and Research, now begin to reveal the relationship between the mitochondria and stem cell proliferation, differentiation and tumorigenesis.

Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Mitochondrial function is understood to play a key role in the ageing process and mitochondrial dysfunction underlies the pathophysiology of various diseases. Whilst much attention has focused on the role of the genetic and epigenetic state on cell function and differentiation in stem cells, little work thus far has addressed the contribution of cell metabolism in stem cell function and activity. New results reported in the March edition of Stem Cells by Mandal et al. from the University of California and Indian Institute of Science Education and Research, now begin to reveal the relationship between the mitochondria and stem cell proliferation, differentiation and tumorigenesis.

Genome-wide Studies reveal that LIN28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Stuart P. Atkinson

The RNA binding protein LIN28 (or LIN28A) is highly expressed in human embryonic stem cells (hESCs) and is often used in the generation of induced pluripotent stem cells (iPSCs) (Yu et al.). It is known to play a role in inhibiting the maturation and promoting the degradation of the Let7 family of microRNAs which are known to promote the expression of genes involved in differentiation. However multiple Let7 independent roles for LIN28 have also been observed, and have prompted a study from the laboratory of Yingqun Huang at the Yale Stem Cell Center presented in the March edition of Stem Cells.

Genome-wide Studies reveal that LIN28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Stuart P. Atkinson

The RNA binding protein LIN28 (or LIN28A) is highly expressed in human embryonic stem cells (hESCs) and is often used in the generation of induced pluripotent stem cells (iPSCs) (Yu et al.). It is known to play a role in inhibiting the maturation and promoting the degradation of the Let7 family of microRNAs which are known to promote the expression of genes involved in differentiation. However multiple Let7 independent roles for LIN28 have also been observed, and have prompted a study from the laboratory of Yingqun Huang at the Yale Stem Cell Center presented in the March edition of Stem Cells.

Multiple roles for Oct4 in induced pluripotency from MEFs and mouse myoblasts

From the March 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Original reports describing the generation of induced pluripotent stem cells (iPSCs) set the foundations of the reprogramming process as the exogenous expression of four transcription factors Oct4, Sox2, Klf4, c-Myc and/or Lin28 and Nanog. Subsequent work has shown that with the use of small molecules direct reprogramming can also be achieved by overexpression of a subset of these factors, in some cases with exogenous Oct4 only. Oct4 expression seems to be integral to the reprogramming process and two articles in the March 2011 issue of Stem Cells now reveal additional roles for Oct4. The first article, by Yuan et al. from Sheng Ding’s laboratory at the Scripps Research Institute in California, reports a new small molecule which can facilitate reprogramming. The authors screened 100 small molecules under TGF-β receptor inhibition in mouse embryonic fibroblasts (MEFs) that had been retrovirally transduced with Oct4 and their results show that AMI-5, an inhibitor of protein arginine methyltransferase (PRMT) activity, could greatly facilitate the reprogramming process.

Multiple roles for Oct4 in induced pluripotency from MEFs and mouse myoblasts

From the March 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Original reports describing the generation of induced pluripotent stem cells (iPSCs) set the foundations of the reprogramming process as the exogenous expression of four transcription factors Oct4, Sox2, Klf4, c-Myc and/or Lin28 and Nanog. Subsequent work has shown that with the use of small molecules direct reprogramming can also be achieved by overexpression of a subset of these factors, in some cases with exogenous Oct4 only. Oct4 expression seems to be integral to the reprogramming process and two articles in the March 2011 issue of Stem Cells now reveal additional roles for Oct4. The first article, by Yuan et al. from Sheng Ding’s laboratory at the Scripps Research Institute in California, reports a new small molecule which can facilitate reprogramming. The authors screened 100 small molecules under TGF-β receptor inhibition in mouse embryonic fibroblasts (MEFs) that had been retrovirally transduced with Oct4 and their results show that AMI-5, an inhibitor of protein arginine methyltransferase (PRMT) activity, could greatly facilitate the reprogramming process.

Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Mitochondrial function is understood to play a key role in the ageing process and mitochondrial dysfunction underlies the pathophysiology of various diseases. Whilst much attention has focused on the role of the genetic and epigenetic state on cell function and differentiation in stem cells, little work thus far has addressed the contribution of cell metabolism in stem cell function and activity. New results reported in the March edition of Stem Cells by Mandal et al. from the University of California and Indian Institute of Science Education and Research, now begin to reveal the relationship between the mitochondria and stem cell proliferation, differentiation and tumorigenesis.

Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Mitochondrial function is understood to play a key role in the ageing process and mitochondrial dysfunction underlies the pathophysiology of various diseases. Whilst much attention has focused on the role of the genetic and epigenetic state on cell function and differentiation in stem cells, little work thus far has addressed the contribution of cell metabolism in stem cell function and activity. New results reported in the March edition of Stem Cells by Mandal et al. from the University of California and Indian Institute of Science Education and Research, now begin to reveal the relationship between the mitochondria and stem cell proliferation, differentiation and tumorigenesis.

Stem Cells Translational Medicine

© AlphaMed Press

Anthony J. Atala, MD, Editor

Mission

STEM CELLS TRANSLATIONAL MEDICINE is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

Vision

The potential of stem cells therapies and regenerative medicine is both provocative and powerful, offering the distinct possibility of eventually repairing or replacing tissues damaged from disease, including certain cancers.

By helping speed expertly executed translations of emerging lab discoveries into legitimate clinical trials and bedside application, STEM CELLS TRANSLATIONAL MEDICINE ultimately will improve patient outcomes.

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