The Experts below are selected from a list of 66228 Experts worldwide ranked by ideXlab platform
Margaret A. Goodell - One of the best experts on this subject based on the ideXlab platform.
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stem Cell Plasticity from transdifferentiation to macrophage fusion
Cell Proliferation, 2004Co-Authors: Fernando D. Camargo, Stuart M Chambers, Margaret A. GoodellAbstract:Abstract. The past 5 years have witnessed an explosion of interest in using adult-derived stem Cells for Cell and gene therapy. This has been driven by a number of findings, in particular, the possibility that some adult stem Cells can differentiate into non-autologous Cell types, and also the discovery of multipotential stem Cells in adult bone marrow. These discoveries suggested a quasi-alchemical nature of Cells derived from adult organs, thus raising new and exciting therapeutic possibilities. Recent data, however, argue against the whole idea of stem Cell ‘Plasticity’, and bring into question the therapeutic strategies based upon this concept. Here, we will review the current state of knowledge in the field and discuss some of the clinical implications.
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stem Cell Plasticity befuddled by the muddle
Current Opinion in Hematology, 2003Co-Authors: Margaret A. GoodellAbstract:In the past 4 years, multiple reports have suggested that stem Cells derived from adult tissues can differentiate outside their tissue of origin, challenging long-accepted tenets of developmental biology. This concept of stem-Cell “Plasticity” has helped to galvanize research on stem Cells due to the myriad therapeutic possibilities. However, there are wide discrepancies in the reported frequencies of so-called transdifferentiation events, from recent reports of negative data to reports of the contribution in some tissues and systems reaching as much as 20%. The evidence for and against stem-Cell Plasticity is reviewed here as well as some of the possible sources of the experimental variation.
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somatic stem Cell Plasticity current evidence and emerging concepts
Experimental Hematology, 2001Co-Authors: Gerald Wulf, Kathyjo A Jackson, Margaret A. GoodellAbstract:In the 19 th century, mammalian tissues were first described to be composed of Cells, leading to the claim that Cells originate exclusively from other Cells (“omnis Cellula a Cellula”) formulated by Virchow and Schwann, respectively [1,2]. At the beginning of the 20 th century, the concept of tissue stem Cells as the basis for tissue regeneration was introduced: analyzing the phylogeny of hematopoiesis in the bone marrow solely based on morphological observations, Pappenheim postulated the existence of an undifferentiated stem Cell (“gemeinsame Stammzelle”) giving rise to the plethora of blood Cells via an intermediate state of progenitor Cells (Fig. 1, [3]). In the 1950s, several groups corroborated the existence of the hematopoietic stem Cell in the bone marrow by showing hematopoietic recovery from transplanted bone marrow after irradiation damage [4–6]. Till and McCulloch later traced hematopoietic repopulation capacity to clonogenic Cells establishing spleen colony-forming units [7]. Subsequently, the concept of tissue regeneration from a small population of resident tissue stem Cells was generally accepted, was extended to nonhematopoietic tissues such as gut and skin [8], and still is our understanding of adult tissue regeneration today, enriched by an immense body of descriptive data. In parallel, the principle of directed Cellular proliferation underlay the understanding of the early stages in embryogenesis and, together with the Cellular movement, led to the discovery of morphogenesis via germ layers in the early embryo [9]. With emerging technologies, it was 33 and 3 years ago that stem Cells with the capacity to differentiate into all tissues of the adult organism were functionally isolated from preimplantation embryos in mice and humans, respectively, and were called embryonic stem (ES) Cells [10–13]. Although the concept of stem Cells in embryogenesis and stem Cells in adult tissue regeneration were initially pursued in conceptually separate approaches, they merged again with the successful cloning of a mammal from the nucleus of an adult tissue Cell 4 years ago [14]. These experiments established that the nuclei of at least some adult Cells were capable of being reprogrammed and spurred several groups to reevaluate the differentiation capacity of adult tissue stem Cells, leading to a number of reports on somatic stem Cell Plasticity over the last 3 years. Here, we will review the current evidence for stem Cell Plasticity. Following the chronology of discoveries, we will start from the broadening developmental potential of bone marrow–derived stem Cells leading to the differentiation capacities of stem Cells from nonhematopoietic tissues. We will discuss some of the potential caveats to the current work, and finally will speculate about the potential underlying mechanisms of transdifferentiation.
Santosh Shenoy - One of the best experts on this subject based on the ideXlab platform.
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Cell Plasticity in cancer a complex interplay of genetic epigenetic mechanisms and tumor micro environment
Surgical Oncology-oxford, 2020Co-Authors: Santosh ShenoyAbstract:Abstract Cell Plasticity, also known as lineage Plasticity is defined as the ability of a Cell to reprogram and change its phenotype identity. Cell Plasticity is context dependent and occurs during the development of an embryo, tissue regeneration, wound healing. However when deregulated and aberrant it also contributes to cancer initiation, progression, metastases and resistance to therapies. Tumors Cells exhibit varying forms of Cell Plasticity in each stage of the disease to evade normal regulation as would have occurred in normal Cell division and homeostasis. Current evidence demonstrates complex interplay between the genes, epigenes, tumor microenvironment and the EMT in Cell reprogramming and cancer Cell Plasticity. Herein we present experimental evidence and evolving new developments in Cell Plasticity in cancer Cells. Additionally “Deregulated/aberrant/hijacked Cell Plasticity” could be considered as an additional hallmark of a cancer. In the future, combining the advances in next generation sequencing and single Cell RNA techniques with evolving AI (artificial intelligence) technologies such as deep learning techniques may predict the trajectories of cancer Cells and assist in navigating through the complex intricacies of the cancers. A durable, precise, personalized oncologic treatment could be a reality.
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Cell Plasticity in cancer: A complex interplay of genetic, epigenetic mechanisms and tumor micro-environment.
Surgical oncology, 2020Co-Authors: Santosh ShenoyAbstract:Cell Plasticity, also known as lineage Plasticity is defined as the ability of a Cell to reprogram and change its phenotype identity. Cell Plasticity is context dependent and occurs during the development of an embryo, tissue regeneration, wound healing. However when deregulated and aberrant it also contributes to cancer initiation, progression, metastases and resistance to therapies. Tumors Cells exhibit varying forms of Cell Plasticity in each stage of the disease to evade normal regulation as would have occurred in normal Cell division and homeostasis. Current evidence demonstrates complex interplay between the genes, epigenes, tumor microenvironment and the EMT in Cell reprogramming and cancer Cell Plasticity. Herein we present experimental evidence and evolving new developments in Cell Plasticity in cancer Cells. Additionally "Deregulated/aberrant/hijacked Cell Plasticity" could be considered as an additional hallmark of a cancer. In the future, combining the advances in next generation sequencing and single Cell RNA techniques with evolving AI (artificial intelligence) technologies such as deep learning techniques may predict the trajectories of cancer Cells and assist in navigating through the complex intricacies of the cancers. A durable, precise, personalized oncologic treatment could be a reality.
Mark W. Jackson - One of the best experts on this subject based on the ideXlab platform.
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Targeting Pancreatic Cancer Cell Plasticity: The Latest in Therapeutics.
Cancers, 2018Co-Authors: Jacob M. Smigiel, Neetha Parameswaran, Mark W. JacksonAbstract:Mortality remains alarmingly high for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC), with 93% succumbing to the disease within five years. The vast majority of PDAC cases are driven by activating mutations in the proto-oncogene KRAS, which results in constitutive proliferation and survival signaling. As efforts to target RAS and its downstream effectors continue, parallel research aimed at identifying novel targets is also needed in order to improve therapeutic options and efficacy. Recent studies demonstrate that self-renewing cancer stem Cells (CSCs) contribute to metastatic dissemination and therapy failure, the causes of mortality from PDAC. Here, we discuss current challenges in PDAC therapeutics, highlight the contribution of mesenchymal/CSC Plasticity to PDAC pathogenesis, and propose that targeting the drivers of Plasticity will prove beneficial. Increasingly, intrinsic oncogenic and extrinsic pro-growth/survival signaling emanating from the tumor microenvironment (TME) are being implicated in the de novo generation of CSC and regulation of tumor Cell Plasticity. An improved understanding of key regulators of PDAC Plasticity is providing new potential avenues for targeting the properties associated with CSC (including enhanced invasion and migration, metastatic outgrowth, and resistance to therapy). Finally, we describe the growing field of therapeutics directed at cancer stem Cells and cancer Cell Plasticity in order to improve the lives of patients with PDAC.
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Oncostatin M promotes cancer Cell Plasticity through cooperative STAT3-SMAD3 signaling
Oncogene, 2017Co-Authors: Damian J. Junk, Jacob M. Smigiel, Neetha Parameswaran, Benjamin L. Bryson, Courtney A. Bartel, Mark W. JacksonAbstract:Increasing evidence supports the idea that cancer Cell Plasticity promotes metastasis and tumor recurrence, resulting in patient mortality. While it is clear that the tumor microenvironment (TME) contributes to cancer Cell Plasticity, the specific TME factors most actively controlling Plasticity remain largely unknown. Here, we performed a screen to identify TME cytokines and growth factors that promote epithelial–mesenchymal Plasticity, and acquisition of cancer stem Cell (CSC) properties. Of 28 TME cytokines and growth factors tested, we identified Oncostatin M (OSM) as the most potent inducer of mesenchymal/CSC properties. OSM-induced Plasticity was Signal Transducer and Activator of Transcription 3 (STAT3)-dependent, and also required a novel intersection with transforming growth factor-β (TGF-β)/SMAD signaling. OSM/STAT3 activation promoted SMAD3 nuclear accumulation, DNA binding and induced SMAD3-dependent transcriptional activity. Suppression of TGF-β receptor activity or ablation of SMAD3 or SMAD4, but not SMAD2, strongly suppressed OSM/STAT3-mediated Plasticity. Moreover, removal of OSM or inhibition of STAT3 or SMAD3 resulted in a marked reversion to a non-invasive, epithelial phenotype. We propose that targeted blockade of the STAT3/SMAD3 axis in tumor Cells may represent a novel therapeutic approach to prevent the Plasticity required for metastatic progression and tumor recurrence.
Ben Z. Stanger - One of the best experts on this subject based on the ideXlab platform.
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Adult Cell Plasticity in vivo: de-differentiation and transdifferentiation are back in style
Nature Reviews Molecular Cell Biology, 2016Co-Authors: Allyson J. Merrell, Ben Z. StangerAbstract:Some terminally differentiated Cells have the capacity to de-differentiate or transdifferentiate under physiological conditions as part of a normal response to injury. Recent insights have been gained into the role of this Cell Plasticity in maintaining tissue and organ homeostasis, and this has important implications for Cell-based therapies. Biologists have long been intrigued by the possibility that Cells can change their identity, a phenomenon known as Cellular Plasticity. The discovery that terminally differentiated Cells can be experimentally coaxed to become pluripotent has invigorated the field, and recent studies have demonstrated that changes in Cell identity are not limited to the laboratory. Specifically, certain adult Cells retain the capacity to de-differentiate or transdifferentiate under physiological conditions, as part of an organ's normal injury response. Recent studies have highlighted the extent to which Cell Plasticity contributes to tissue homeostasis, findings that have implications for Cell-based therapy. Mature, terminally differentiated Cells have the capacity to de-differentiate or transdifferentiate in vivo . De-differentiation and transdifferentiation can be forced experimentally, but these processes also occur physiologically in response to tissue injury and/or Cell loss. Cellular Plasticity involves the repression of genes associated with the previous Cell type, as well as activation of genes associated with the new Cell type. Cells may occupy 'intermediate' identity states while undergoing de-differentiation or transdifferentiation. Such changes can be reversible. Cellular Plasticity can be driven by factors that induce a new identity or by the loss of inhibitory factors that maintain the old identity.
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Adult Cell Plasticity in vivo : de-differentiation and transdifferentiation are back in style
Nature reviews. Molecular cell biology, 2016Co-Authors: Allyson J. Merrell, Ben Z. StangerAbstract:Some terminally differentiated Cells have the capacity to de-differentiate or transdifferentiate under physiological conditions as part of a normal response to injury. Recent insights have been gained into the role of this Cell Plasticity in maintaining tissue and organ homeostasis, and this has important implications for Cell-based therapies.
Purificación Muñoz - One of the best experts on this subject based on the ideXlab platform.
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Tumor-Infiltrating Immunosuppressive Cells in Cancer-Cell Plasticity, Tumor Progression and Therapy Response
Cancer Microenvironment, 2019Co-Authors: Laura Lorenzo-sanz, Purificación MuñozAbstract:In most tumors, cancer Cells show the ability to dynamically transit from a non-cancer stem-like Cell to a cancer stem-like Cell (CSC) state and vice versa. This Cell Plasticity has been associated with the epithelial-to-mesenchymal transition program (EMT) and can be regulated by tumor Cell-intrinsic mechanisms and complex interactions with various tumor microenvironment (TME) components. These interactions favor the generation of a specific “CSC niche” that helps maintain the main properties, phenotypic Plasticity and metastatic potential of this subset of tumor Cells. For this reason, TME has been recognized as an important promoter of tumor progression and therapy resistance. Tumors have evolved a network of immunosuppressive mechanisms that limits the cytotoxic T Cell response to cancer Cells. Some key players in this network are tumor-associated macrophages, myeloid-derived suppressor Cells and regulatory T Cells, which not only favor a pro-tumoral and immunosuppressive environment that supports tumor growth and immune evasion, but also negatively influences immunotherapy. Here, we review the relevance of cytokines and growth factors provided by immunosuppressive immune Cells in regulating cancer-Cell Plasticity. We also discuss how cancer Cells remodel their own niche to promote proliferation, stemness and EMT, and escape immune surveillance. A better understanding of CSC-TME crosstalk signaling will enable the development of effective targeted or immune therapies that block tumor growth and metastasis.
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Cancer Cell Plasticity: Impact on tumor progression and therapy response.
Seminars in cancer biology, 2018Co-Authors: Victoria Da Silva-diz, Laura Lorenzo-sanz, Adrià Bernat-peguera, Marta Lopez-cerda, Purificación MuñozAbstract:Abstract Most tumors exhibit intra-tumor heterogeneity, which is associated with disease progression and an impaired response to therapy. Cancer Cell Plasticity has been proposed as being an important mechanism that, along with genetic and epigenetic alterations, promotes cancer Cell diversity and contributes to intra-tumor heterogeneity. Plasticity endows cancer Cells with the capacity to shift dynamically between a differentiated state, with limited tumorigenic potential, and an undifferentiated or cancer stem-like Cell (CSC) state, which is responsible for long-term tumor growth. In addition, it confers the ability to transit into distinct CSC states with different competence to invade, disseminate and seed metastasis. Cancer Cell Plasticity has been linked to the epithelial-to-mesenchymal transition program and relies not only on Cell-autonomous mechanisms, but also on signals provided by the tumor microenvironment and/or induced in response to therapy. We provide an overview of the dynamic transition for cancer Cell states, the mechanisms governing Cell Plasticity and their impact on tumor progression, metastasis and therapy response. Understanding the mechanisms involved in cancer Cell Plasticity will provide insights for establishing new therapeutic interventions.