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Single Transcription Factor Reprogramming of Hair Follicle Dermal Papilla Cells to Induced Pluripotent Stem Cells

From the June 2011 Issue of Stem Cells
Paper Commentary by Stuart P. Atkinson

A safe and accessible source of somatic cells which are amenable to reprogramming and the generation of induced pluripotent stem cells (iPSCs) is currently very much sought after. While some adult stem cell sources are readily reprogrammable with one or two factors, neural progenitor cells are not a readily accessible population (Kim et al and Kim et al). So, can we find another source? Skin dermal papilla (DP) cells are a specialised mesenchymal stem cell type involved in hair morphogenesis and regeneration. Previous studies into the reprogramming of DP cells have shown that Sox2, Klf4 and Myc were already expressed and so DP cells could be reprogrammed using forced expression of Oct4 and Klf4 alone (Rendl et al and Tsai et al). The next step was to try the reprogramming process with only one factor, and a study (Tsai et al) which is presented in the June edition of Stem cells from the group of Michael Rendl at the Mount Sinai School of Medicine, New York, USA does just that – with Oct4.

Single Transcription Factor Reprogramming of Hair Follicle Dermal Papilla Cells to Induced Pluripotent Stem Cells

From the June 2011 Issue of Stem Cells
Paper Commentary by Stuart P. Atkinson

A safe and accessible source of somatic cells which are amenable to reprogramming and the generation of induced pluripotent stem cells (iPSCs) is currently very much sought after. While some adult stem cell sources are readily reprogrammable with one or two factors, neural progenitor cells are not a readily accessible population (Kim et al and Kim et al). So, can we find another source? Skin dermal papilla (DP) cells are a specialised mesenchymal stem cell type involved in hair morphogenesis and regeneration. Previous studies into the reprogramming of DP cells have shown that Sox2, Klf4 and Myc were already expressed and so DP cells could be reprogrammed using forced expression of Oct4 and Klf4 alone (Rendl et al and Tsai et al). The next step was to try the reprogramming process with only one factor, and a study (Tsai et al) which is presented in the June edition of Stem cells from the group of Michael Rendl at the Mount Sinai School of Medicine, New York, USA does just that – with Oct4.

Snail and the microRNA-200 Family Act in Opposition to Regulate Epithelial-to-Mesenchymal Transition and Germ Layer Fate Restriction in Differentiating ESCs

From the May 2011 Issue of Stem Cells
Paper Commentary by Stuart P. Atkinson

Recent high impact studies have shown that the reprogramming of somatic cells towards pluripotency requires a mesenchymal-to-epithelial transition (MET) (Li et al and Samavarchi-Tehrani et al) which is in part mediated by the function of microRNA (miRNA) species (Liao et al and Subramanyam et al). However, the role of the epithelial-to-mesenchymal transition (EMT) during the differentiation of embryonic stem cells (ESCs) and its potential role in fate commitment have not yet been studied in great detail. Now, in a study published in the May edition of Stem Cells, researchers from the lab of Kenneth M. Murphy at the Washington University School of Medicine, St. Louis, Missouri, USA have begun to unravel the important pathways required for the early differentiation and fate commitment in ESC, and indicate an important role for the tight regulation of EMT controlled by miRNA (Gill et al).

Snail and the microRNA-200 Family Act in Opposition to Regulate Epithelial-to-Mesenchymal Transition and Germ Layer Fate Restriction in Differentiating ESCs

From the May 2011 Issue of Stem Cells
Paper Commentary by Stuart P. Atkinson

Recent high impact studies have shown that the reprogramming of somatic cells towards pluripotency requires a mesenchymal-to-epithelial transition (MET) (Li et al and Samavarchi-Tehrani et al) which is in part mediated by the function of microRNA (miRNA) species (Liao et al and Subramanyam et al). However, the role of the epithelial-to-mesenchymal transition (EMT) during the differentiation of embryonic stem cells (ESCs) and its potential role in fate commitment have not yet been studied in great detail. Now, in a study published in the May edition of Stem Cells, researchers from the lab of Kenneth M. Murphy at the Washington University School of Medicine, St. Louis, Missouri, USA have begun to unravel the important pathways required for the early differentiation and fate commitment in ESC, and indicate an important role for the tight regulation of EMT controlled by miRNA (Gill et al).

Reprogramming of Postnatal Neurons into Induced Pluripotent Stem Cells by Defined Factors

From the June 2011 Issue of Stem Cells
Paper Commentary by Stuart P. Atkinson

The field of induced pluripotent stem cells (iPSCs) grows and expands with every passing day, fuelled by the seemingly graspable prize of a bona fide source of patient-specific pluripotent cells for regenerative medicine, be it for cell replacement therapy, drug screening or developmental studies. However underlying questions still remain pertaining to the cell type which undergoes reprogramming and ultimately their long term usefulness. In a new study (Kim et al) published in the June edition of Stem Cells, researchers from the laboratory of Rudolf Jaenisch at Massachusetts Institute of Technology, Cambridge, now try to answer some of these questions. Although iPSC have been generated from an increasing number of somatic cell types, the heterogeneity and the lack of markers for said cell types has not yet allowed the thorough study of the reprogramming of terminally differentiated somatic cells.

Reprogramming of Postnatal Neurons into Induced Pluripotent Stem Cells by Defined Factors

From the June 2011 Issue of Stem Cells
Paper Commentary by Stuart P. Atkinson

The field of induced pluripotent stem cells (iPSCs) grows and expands with every passing day, fuelled by the seemingly graspable prize of a bona fide source of patient-specific pluripotent cells for regenerative medicine, be it for cell replacement therapy, drug screening or developmental studies. However underlying questions still remain pertaining to the cell type which undergoes reprogramming and ultimately their long term usefulness. In a new study (Kim et al) published in the June edition of Stem Cells, researchers from the laboratory of Rudolf Jaenisch at Massachusetts Institute of Technology, Cambridge, now try to answer some of these questions. Although iPSC have been generated from an increasing number of somatic cell types, the heterogeneity and the lack of markers for said cell types has not yet allowed the thorough study of the reprogramming of terminally differentiated somatic cells.

Differentiation of Swine iPSC into Rod Photoreceptors and Their Integration into the Retina

From the May 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Stem cell therapy remains one of the most promising options for restoration of the degenerative retina. Featured in the May edition of Stem Cells are two articles (Zhou et al. and Kokkinaki et al.) which demonstrate that induced pluripotent stem cells (iPSC) can be differentiated into various components of the mature retina. These articles individually address two important considerations; the first, discussed herein, shows that iPSC-derived photoreceptors can integrate and start to develop features typical of morphological maturation following transplantation into the degenerative retina, and the other that retinal pigmented epithelium (RPE) generated from iPSC is capable of acting in a functional manner (see the link to this paper commentary on the Stem Cell Portal homepage). The light-sensitive photoreceptors reside in the outer nuclear layer (ONL) of the retina and are supported by the underlying RPE. The RPE transfers oxygen and nutrients to the photoreceptors from the choroidal blood supply and performs many functions essential for the health of the photoreceptors, including phagocytosis of shed photoreceptor outer segments and the removal of the waste products of the visual cycle. The article by Zhou et al. from the Department of Ophthalmology at Central South University in China and multiple collaborative centres at the University of Louisville, describes the differentiation of cells from a swine iPSC line into rod photoreceptors and their integration within a swine model of retinal degeneration.

Differentiation of Swine iPSC into Rod Photoreceptors and Their Integration into the Retina

From the May 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Stem cell therapy remains one of the most promising options for restoration of the degenerative retina. Featured in the May edition of Stem Cells are two articles (Zhou et al. and Kokkinaki et al.) which demonstrate that induced pluripotent stem cells (iPSC) can be differentiated into various components of the mature retina. These articles individually address two important considerations; the first, discussed herein, shows that iPSC-derived photoreceptors can integrate and start to develop features typical of morphological maturation following transplantation into the degenerative retina, and the other that retinal pigmented epithelium (RPE) generated from iPSC is capable of acting in a functional manner (see the link to this paper commentary on the Stem Cell Portal homepage). The light-sensitive photoreceptors reside in the outer nuclear layer (ONL) of the retina and are supported by the underlying RPE. The RPE transfers oxygen and nutrients to the photoreceptors from the choroidal blood supply and performs many functions essential for the health of the photoreceptors, including phagocytosis of shed photoreceptor outer segments and the removal of the waste products of the visual cycle. The article by Zhou et al. from the Department of Ophthalmology at Central South University in China and multiple collaborative centres at the University of Louisville, describes the differentiation of cells from a swine iPSC line into rod photoreceptors and their integration within a swine model of retinal degeneration.

Human iPS-derived Retinal Pigment Epithelium (RPE) Cells Exhibit Transport, Membrane Potential, Polarized VEGF Secretion and Gene Expression Pattern Similar to Native RPE

From the May 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Complimentary to another article involving the retina, also featured in the May edition of Stem Cells, the potential for induced pluripotent stem cells (iPSC) to generate replacement retinal components is further demonstrated in an article by Kokkinaki et al. from Georgetown University in Washington DC, which reports that iPSCs can be differentiated into retinal pigmented epithelium (RPE) that can perform many of the normal functions of native RPE. The health of the light sensitive photoreceptors that reside at the back of the retina are dependent on a functional RPE, in fact the two cell types are interdependent. Within the eye, the apical membrane of the RPE cells face the outer segments of the photoreceptors and not only phagocytose shed photoreceptor outer segments but perform a number of other functions including the release of growth factors and isomerisation of retinal from the phototransduction cycle. Various forms of retinal disease require the replacement of dysfunctional RPE with new functional RPE, such as age-related macular degeneration (AMD), where impaired RPE function in turn causes the death of macular photoreceptors. Many reports have shown the facile generation of RPE from both human embryonic stem cells (hESC) and induced pluripotent stem cells (RPE), making these cell types an attractive source of replacement RPE.

Human iPS-derived Retinal Pigment Epithelium (RPE) Cells Exhibit Transport, Membrane Potential, Polarized VEGF Secretion and Gene Expression Pattern Similar to Native RPE

From the May 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Complimentary to another article involving the retina, also featured in the May edition of Stem Cells, the potential for induced pluripotent stem cells (iPSC) to generate replacement retinal components is further demonstrated in an article by Kokkinaki et al. from Georgetown University in Washington DC, which reports that iPSCs can be differentiated into retinal pigmented epithelium (RPE) that can perform many of the normal functions of native RPE. The health of the light sensitive photoreceptors that reside at the back of the retina are dependent on a functional RPE, in fact the two cell types are interdependent. Within the eye, the apical membrane of the RPE cells face the outer segments of the photoreceptors and not only phagocytose shed photoreceptor outer segments but perform a number of other functions including the release of growth factors and isomerisation of retinal from the phototransduction cycle. Various forms of retinal disease require the replacement of dysfunctional RPE with new functional RPE, such as age-related macular degeneration (AMD), where impaired RPE function in turn causes the death of macular photoreceptors. Many reports have shown the facile generation of RPE from both human embryonic stem cells (hESC) and induced pluripotent stem cells (RPE), making these cell types an attractive source of replacement RPE.

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