The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform
Josipa Bilic - One of the best experts on this subject based on the ideXlab platform.
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identification of a specific reprogramming associated epigenetic signature in human induced pluripotent stem Cells
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Sergio Ruiz, Nuria Montserrat, Dinh Diep, Athurva Gore, Athanasia D Panopoulos, Nongluk Plongthongkum, Sachin Kumar, Holim Fung, Alessandra Giorgetti, Josipa BilicAbstract:Generation of human induced pluripotent stem Cells (hiPSCs) by the expression of specific transcription factors depends on successful epigenetic reprogramming to a pluripotent state. Although hiPSCs and human embryonic stem Cells (hESCs) display a similar epigenome, recent reports demonstrated the persistence of specific epigenetic marks from the Somatic Cell Type of origin and aberrant methylation patterns in hiPSCs. However, it remains unknown whether the use of different Somatic Cell sources, encompassing variable levels of selection pressure during reprogramming, influences the level of epigenetic aberrations in hiPSCs. In this work, we characterized the epigenomic integrity of 17 hiPSC lines derived from six different Cell Types with varied reprogramming efficiencies. We demonstrate that epigenetic aberrations are a general feature of the hiPSC state and are independent of the Somatic Cell source. Interestingly, we observe that the reprogramming efficiency of Somatic Cell lines inversely correlates with the amount of methylation change needed to acquire pluripotency. Additionally, we determine that both shared and line-specific epigenetic aberrations in hiPSCs can directly translate into changes in gene expression in both the pluripotent and differentiated states. Significantly, our analysis of different hiPSC lines from multiple Cell Types of origin allow us to identify a reprogramming-specific epigenetic signature comprised of nine aberrantly methylated genes that is able to segregate hESC and hiPSC lines regardless of the Somatic Cell source or differentiation state.
Andrew Koff - One of the best experts on this subject based on the ideXlab platform.
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Somatic Cell Type specific gene transfer reveals a tumor promoting function for p21waf1 cip1
The EMBO Journal, 2007Co-Authors: Margaret Leversha, Carlos Cordoncardo, Ronald Ghossein, Bhuvanesh Singh, Eric C Holland, Andrew KoffAbstract:How proteins participate in tumorigenesis can be obscured by their multifunctional nature. For example, depending on the Cellular context, the cdk inhibitors can affect Cell proliferation, Cell motility, apoptosis, receptor tyrosine kinase signaling, and transcription. Thus, to determine how a protein contributes to tumorigenesis, we need to evaluate which functions are required in the developing tumor. Here we demonstrate that the RCAS/TvA system, originally developed to introduce oncogenes into Somatic Cells of mice, can be adapted to allow us to define the contribution that different functional domains make to tumor development. Studying the development of growth-factor-induced oligodendroglioma, we identified a critical role for the Cy elements in p21, and we showed that cyclin D1T286A, which accumulates in the nucleus of p21-deficient Cells and binds to cdk4, could bypass the requirement for p21 during tumor development. These genetic results suggest that p21 acts through the cyclin D1–cdk4 complex to support tumor growth, and establish the utility of using a Somatic Cell modeling system for defining the contribution proteins make to tumor development.
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Somatic Cell Type specific gene transfer reveals a tumor‐promoting function for p21Waf1/Cip1
The EMBO Journal, 2007Co-Authors: Margaret Leversha, Ronald Ghossein, Bhuvanesh Singh, Eric C Holland, Carlos Cordon-cardo, Andrew KoffAbstract:How proteins participate in tumorigenesis can be obscured by their multifunctional nature. For example, depending on the Cellular context, the cdk inhibitors can affect Cell proliferation, Cell motility, apoptosis, receptor tyrosine kinase signaling, and transcription. Thus, to determine how a protein contributes to tumorigenesis, we need to evaluate which functions are required in the developing tumor. Here we demonstrate that the RCAS/TvA system, originally developed to introduce oncogenes into Somatic Cells of mice, can be adapted to allow us to define the contribution that different functional domains make to tumor development. Studying the development of growth-factor-induced oligodendroglioma, we identified a critical role for the Cy elements in p21, and we showed that cyclin D1T286A, which accumulates in the nucleus of p21-deficient Cells and binds to cdk4, could bypass the requirement for p21 during tumor development. These genetic results suggest that p21 acts through the cyclin D1–cdk4 complex to support tumor growth, and establish the utility of using a Somatic Cell modeling system for defining the contribution proteins make to tumor development.
Nuria Montserrat - One of the best experts on this subject based on the ideXlab platform.
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Lineage Reprogramming Toward Kidney Regeneration
Kidney Transplantation Bioengineering and Regeneration, 2017Co-Authors: Nuria Montserrat, Josep M. Campistol, Juan Carlos Izpisua BelmonteAbstract:Summary We have known for decades that it is possible to switch the phenoType of one Somatic Cell Type into another. Such epigenetic rewiring processes can be artificially managed and even reversed by using a defined set of transcription factors. Lineage reprogramming is very often defined as a process of converting one Cell Type into another without going through a pluripotent state, providing great promise for regenerative medicine. However, the identification of key transcription factors for lineage reprogramming is limited, due to the exhaustive and expensive experimental processes. Accumulating knowledge of genetic and epigenetic regulatory networks that are critical for defining a specific lineage provides unprecedented opportunities to model and predict pioneering factors that may drive directional lineage reprogramming to obtain the desired Cell Type.
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identification of a specific reprogramming associated epigenetic signature in human induced pluripotent stem Cells
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Sergio Ruiz, Nuria Montserrat, Dinh Diep, Athurva Gore, Athanasia D Panopoulos, Nongluk Plongthongkum, Sachin Kumar, Holim Fung, Alessandra Giorgetti, Josipa BilicAbstract:Generation of human induced pluripotent stem Cells (hiPSCs) by the expression of specific transcription factors depends on successful epigenetic reprogramming to a pluripotent state. Although hiPSCs and human embryonic stem Cells (hESCs) display a similar epigenome, recent reports demonstrated the persistence of specific epigenetic marks from the Somatic Cell Type of origin and aberrant methylation patterns in hiPSCs. However, it remains unknown whether the use of different Somatic Cell sources, encompassing variable levels of selection pressure during reprogramming, influences the level of epigenetic aberrations in hiPSCs. In this work, we characterized the epigenomic integrity of 17 hiPSC lines derived from six different Cell Types with varied reprogramming efficiencies. We demonstrate that epigenetic aberrations are a general feature of the hiPSC state and are independent of the Somatic Cell source. Interestingly, we observe that the reprogramming efficiency of Somatic Cell lines inversely correlates with the amount of methylation change needed to acquire pluripotency. Additionally, we determine that both shared and line-specific epigenetic aberrations in hiPSCs can directly translate into changes in gene expression in both the pluripotent and differentiated states. Significantly, our analysis of different hiPSC lines from multiple Cell Types of origin allow us to identify a reprogramming-specific epigenetic signature comprised of nine aberrantly methylated genes that is able to segregate hESC and hiPSC lines regardless of the Somatic Cell source or differentiation state.
Deqiang Sun - One of the best experts on this subject based on the ideXlab platform.
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Human pluripotent stem Cell-derived chondroprogenitors for cartilage tissue engineering
Cellular and Molecular Life Sciences, 2020Co-Authors: Naoki Nakayama, Azim Pothiawala, John Y. Lee, Nadine Matthias, Katsutsugu Umeda, Bryan K. Ang, Johnny Huard, Yun Huang, Deqiang SunAbstract:The cartilage of joints, such as meniscus and articular cartilage, is normally long lasting (i.e., permanent). However, once damaged, especially in large animals and humans, joint cartilage is not spontaneously repaired. Compensating the lack of repair activity by supplying cartilage-(re)forming Cells, such as chondrocytes or mesenchymal stromal Cells, or by transplanting a piece of normal cartilage, has been the basis of therapy for biological restoration of damaged joint cartilage. Unfortunately, current biological therapies face problems on a number of fronts. The joint cartilage is generated de novo from a specialized Cell Type, termed a ‘joint progenitor’ or ‘interzone Cell’ during embryogenesis. Therefore, embryonic chondroprogenitors that mimic the property of joint progenitors might be the best Type of Cell for regenerating joint cartilage in the adult. Pluripotent stem Cells (PSCs) are expected to differentiate in culture into any Somatic Cell Type through processes that mimic embryogenesis, making human (h)PSCs a promising source of embryonic chondroprogenitors. The major research goals toward the clinical application of PSCs in joint cartilage regeneration are to (1) efficiently generate lineage-specific chondroprogenitors from hPSCs, (2) expand the chondroprogenitors to the number needed for therapy without loss of their chondrogenic activity, and (3) direct the in vivo or in vitro differentiation of the chondroprogenitors to articular or meniscal (i.e., permanent) chondrocytes rather than growth plate (i.e., transient) chondrocytes. This review is aimed at providing the current state of research toward meeting these goals. We also include our recent achievement of successful generation of “permanent-like” cartilage from long-term expandable, hPSC-derived ectomesenchymal chondroprogenitors.
Kimberly M. Christian - One of the best experts on this subject based on the ideXlab platform.
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Using Induced Pluripotent Stem Cells to Investigate Complex Genetic Psychiatric Disorders
Current Behavioral Neuroscience Reports, 2016Co-Authors: Stephanie J. Temme, Brady J. Maher, Kimberly M. ChristianAbstract:Purpose of Review Induced pluripotent stem Cells (iPSCs) can be generated from human patient tissue samples, differentiated into any Somatic Cell Type, and studied under controlled culture conditions. We review how iPSCs are used to investigate genetic factors and biological mechanisms underlying psychiatric disorders, and considerations for synthesizing data across studies. Recent Findings Results from patient specific-iPSC studies often reveal Cellular phenoTypes consistent with postmortem and brain imaging studies. Unpredicted findings illustrate the power of iPSCs as a discovery tool, but may also be attributable to limitations in modeling dynamic neural networks or difficulty in identifying the most affected neural subType or developmental stage. Summary Technological advances in differentiation protocols and organoid generation will enhance our ability to model the salient pathology underlying psychiatric disorders using iPSCs. The field will also benefit from context-driven interpretations of iPSC studies that recognize all potential sources of variability, including differences in patient symptomatology, genetic risk factors, and affected Cellular subType.
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Using Induced Pluripotent Stem Cells to Investigate Complex Genetic Psychiatric Disorders
Current Behavioral Neuroscience Reports, 2016Co-Authors: Stephanie J. Temme, Brady J. Maher, Kimberly M. ChristianAbstract:Purpose of Review Induced pluripotent stem Cells (iPSCs) can be generated from human patient tissue samples, differentiated into any Somatic Cell Type, and studied under controlled culture conditions. We review how iPSCs are used to investigate genetic factors and biological mechanisms underlying psychiatric disorders, and considerations for synthesizing data across studies.