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Rita A Kandel - One of the best experts on this subject based on the ideXlab platform.
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adseverin an actin binding protein regulates articular chondrocyte phenotype
Journal of Tissue Engineering and Regenerative Medicine, 2019Co-Authors: Rita A Kandel, Justin Parreno, Michael Glogauer, Byron Chan, Yongqiang WangAbstract:Chondrocytes dedifferentiate as a result of monolayer culture for cell number expansion. This is associated with the development of an elongated shape, increased actin polymerization, development of stress fibres, and expression of contractile molecules. Given the changes in actin status with Dedifferentiation, the hypothesis of this study was that adseverin, an actin severing and capping protein, plays a role in regulating chondrocyte phenotype and function. This study reports that serial passaging of articular chondrocytes in monolayer culture resulted in loss of adseverin protein expression as early as Day 14 of culture and remained repressed in Passage 2 (P2) cells. Knockdown of adseverin by siRNA in primary chondrocytes promoted an increase in cell size and an elongated shape, actin stress fibres, decreased G-/F-actin ratio, and increased number of actin-free barbed ends. The cells also showed increased expression of the contractile genes and proteins, vinculin and α-smooth muscle actin, and increased ability to contract collagen gels. These are all features of Dedifferentiation. These effects were due to adseverin as adseverin overexpression following transfection of the green fluorescent protein-adseverin plasmid partially reversed all of these changes in P2 chondrocytes. Furthermore, sox9 and aggrecan chondrogenic gene expression was upregulated, and collagen type I genes expression was downregulated with adseverin overexpression. The change in aggrecan mRNA expression had functional consequence as these cells exhibited increased total proteoglycan synthesis. These findings demonstrate that adseverin regulates features indicative of redifferentiation in passaged articular chondrocytes through modulation of the actin cytoskeleton status and potentially may regulate the maintenance of phenotype in primary chondrocytes.
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interplay between cytoskeletal polymerization and the chondrogenic phenotype in chondrocytes passaged in monolayer culture
Journal of Anatomy, 2017Co-Authors: Mortah Nabavi Niaki, Justin Parreno, Katarina Andrejevic, Amy Jiang, Rita A KandelAbstract:Tubulin and actin exist as monomeric units that polymerize to form either microtubules or filamentous actin. As the polymerization status (monomeric/polymeric ratio) of tubulin and/or actin have been shown to be important in regulating gene expression and phenotype in non-chondrocyte cells, the objective of this study was to examine the role of cytoskeletal polymerization on the chondrocyte phenotype. We hypothesized that actin and/or tubulin polymerization status modulates the chondrocyte phenotype during monolayer culture as well as in 3D culture during redifferentiation. To test this hypothesis, articular chondrocytes were grown and passaged in 2D monolayer culture. Cell phenotype was investigated by assessing cell morphology (area and circularity), actin/tubulin content, organization and polymerization status, as well as by determination of proliferation, fibroblast and cartilage matrix gene expression with passage number. Bovine chondrocytes became larger, more elongated, and had significantly (P 0.05) modulated, actin polymerization was increased in bovine P2 cells. Actin depolymerization, but not tubulin depolymerization, promoted the chondrocyte phenotype by inducing cell rounding, increasing aggrecan and reducing COL1 expression. Knockdown of actin depolymerization factor, cofilin, in these cells induced further P2 cell actin polymerization and increased COL1 gene expression. To confirm that actin status regulated COL1 gene expression in human P2 chondrocytes, human P2 chondrocytes were exposed to cytochalasin D. Cytochalasin D decreased COL1 gene expression in human passaged chondrocytes. Furthermore, culture of bovine P2 chondrocytes in 3D culture on porous bone substitute resulted in actin depolymerization, which correlated with decreased expression of COL1 and proliferation molecules. In 3D cultures, aggrecan gene expression was increased by cytochalasin D treatment and COL1 was further decreased. These results reveal that actin polymerization status regulates chondrocyte Dedifferentiation. Reorganization of the cytoskeleton by actin depolymerization appears to be an active regulatory mechanism for redifferentiation of passaged chondrocytes.
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in vitro cartilage tissue formation by co culture of primary and passaged chondrocytes
Tissue Engineering, 2007Co-Authors: Lu Gan, Rita A KandelAbstract:Passaging chondrocytes to increase cell number is one way to overcome the major limitation to cartilage tissue engineering, which is obtaining sufficient numbers of chondrocytes to form large amounts of tissue. Because neighboring cells can influence cell phenotype and because passaging induces Dedifferentiation, we examined whether coculture of primary and passaged bovine articular chondrocytes in 3-dimensional culture would form cartilage tissue in vitro. Chondrocytes passaged in monolayer culture up to 4 times were mixed with primary (nonpassaged) chondrocytes (5–40% of total cell number) and grown on filter inserts for up to 4 weeks. Passaged cells alone did not form cartilage, but with the addition of increasing numbers of primary chondrocytes, up to 20%, there was an increase in cartilage tissue formation as determined histologically and biochemically and demonstrated by increasing proteoglycan and collagen accumulation. The passaged cells appeared to be undergoing redifferentiation, as indicated by...
Akira Iwase - One of the best experts on this subject based on the ideXlab platform.
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PRC2 represses Dedifferentiation of mature somatic cells in Arabidopsis.
Nature plants, 2015Co-Authors: Momoko Ikeuchi, Akira Iwase, Bart Rymen, Hirofumi Harashima, Michitaro Shibata, Mariko Ohnuma, Christian Breuer, Ana Karina Morao, Miguel De Lucas, Lieven De VeylderAbstract:Plant somatic cells are generally acknowledged to retain totipotency, the potential to develop into any cell type within an organism. This astonishing plasticity may contribute to a high regenerative capacity on severe damage, but how plants control this potential during normal post-embryonic development remains largely unknown(1,2). Here we show that POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a chromatin regulator that maintains gene repression through histone modification, prevents Dedifferentiation of mature somatic cells in Arabidopsis thaliana roots. Loss-of-function mutants in PRC2 subunits initially develop unicellular root hairs indistinguishable from those in wild type but fail to retain the differentiated state, ultimately resulting in the generation of an unorganized cell mass and somatic embryos from a single root hair. Strikingly, mutant root hairs complete the normal endoreduplication programme, increasing their nuclear ploidy, but subsequently reinitiate mitotic division coupled with successive DNA replication. Our data show that the WOUND INDUCED Dedifferentiation3 (WIND3) and LEAFY COTYLEDON2 (LEC2) genes are among the PRC2 targets involved in this reprogramming, as their ectopic overexpression partly phenocopies the Dedifferentiation phenotype of PRC2 mutants. These findings unveil the pivotal role of PRC2-mediated gene repression in preventing unscheduled reprogramming of fully differentiated plant cells.
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arabidopsis wind1 induces callus formation in rapeseed tomato and tobacco
Plant Signaling & Behavior, 2013Co-Authors: Akira Iwase, Momoko Ikeuchi, Mariko Ohnuma, Nobutaka Mitsuda, Chie Koizuka, Koich Kawamoto, Jun Imamura, Hiroshi Ezura, Keiko SugimotoAbstract:The capacity to promote cell Dedifferentiation is widespread among plant species. We have recently reported that an AP2/ERF transcription factor WOUND INDUCED Dedifferentiation 1 (WIND1) and its paralogues, WIND2–4, promote cell Dedifferentiation in Arabidopsis (Arabidopsis thaliana). Phylogenetic analyses suggest that AtWIND1 orthologs are found in land plants and that the shared peptide motifs between Arabidopsis paralogues are conserved in putative orthologs in dicotyledonous and monocotyledonous plants. In this study we show that AtWIND1 chemically induced rapeseed and tomato, as well as AtWIND1 constitutively expressed tobacco, promote callus formation on phytohormone-free medium. Our results suggest that the WIND1-mediated signaling cascade to promote cell Dedifferentiation might be conserved in at least several species of Brassicaceae and Solanaceae.
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wind1 a key molecular switch for plant cell Dedifferentiation
Plant Signaling & Behavior, 2011Co-Authors: Akira Iwase, Masaru Ohmetakagi, Keiko SugimotoAbstract:Cellular Dedifferentiation is often observed in both plants and animals at an early step of wound-induced regeneration. Some plant species develop callus, a mass of unorganised cells, after wounding and this response is thought to involve cell Dedifferentiation since callus cells are usually ready to exert totipotency, an ability to regenerate any new organ including somatic embryos. It is well established that a balance of the two plant hormones, auxin and cytokinin, is central in controlling plant cell Dedifferentiation and subsequent redifferentiation but molecular mechanisms underlying these processes are still unclear. In a recent study we reported that an AP2/ERF transcription factor WOUND INDUCED Dedifferentiation 1 (WIND1) and its close homologs, WIND2–4, are induced by wounding and that they promote cell Dedifferentiation in Arabidopsis. Our data show that WIND proteins are required to activate the local cytokinin response at the wound site.
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the ap2 erf transcription factor wind1 controls cell Dedifferentiation in arabidopsis
Current Biology, 2011Co-Authors: Akira Iwase, Nobutaka Mitsuda, Tomotsugu Koyama, Keiichiro Hiratsu, Mikiko Kojima, Takashi Arai, Yasunori Inoue, Motoaki SekiAbstract:Many multicellular organisms have remarkable capability to regenerate new organs after wounding. As a first step of organ regeneration, adult somatic cells often dedifferentiate to reacquire cell proliferation potential, but mechanisms underlying this process remain unknown in plants. Here we show that an AP2/ERF transcription factor, WOUND INDUCED Dedifferentiation 1 (WIND1), is involved in the control of cell Dedifferentiation in Arabidopsis. WIND1 is rapidly induced at the wound site, and it promotes cell Dedifferentiation and subsequent cell proliferation to form a mass of pluripotent cells termed callus. We further demonstrate that ectopic overexpression of WIND1 is sufficient to establish and maintain the dedifferentiated status of somatic cells without exogenous auxin and cytokinin, two plant hormones that are normally required for cell Dedifferentiation. In vivo imaging of a synthetic cytokinin reporter reveals that wounding upregulates the B-type ARABIDOPSIS RESPONSE REGULATOR (ARR)-mediated cytokinin response and that WIND1 acts via the ARR-dependent signaling pathway to promote cell Dedifferentiation. This study provides novel molecular insights into how plants control cell Dedifferentiation in response to wounding.
Barak Blum - One of the best experts on this subject based on the ideXlab platform.
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the anna karenina model of β cell maturation in development and their Dedifferentiation in type 1 and type 2 diabetes
Diabetes, 2021Co-Authors: Sutichot D Nimkulrat, Matthew N Bernstein, Jared Brown, Christina Kendziorski, Barak BlumAbstract:Loss of mature β cell function and identity, or β cell Dedifferentiation, is seen in both type 1 and type 2 diabetes. Two competing models explain β cell Dedifferentiation in diabetes. In the first model, β cells dedifferentiate in the reverse order of their developmental ontogeny. This model predicts that dedifferentiated β cells resemble β cell progenitors. In the second model, β cell Dedifferentiation depends on the type of diabetogenic stress. This model, which we call the “Anna Karenina” model, predicts that in each type of diabetes, β cells dedifferentiate in their own way, depending on how their mature identity is disrupted by any particular diabetogenic stress. We directly tested the two models using a β cell-specific lineage-tracing system coupled with RNA-sequencing in mice. We constructed a multidimensional map of β cell transcriptional trajectories during the normal course of β cell postnatal development and during their Dedifferentiation in models of both type 1 diabetes (NOD) and type 2 diabetes (BTBR-Lepob/ob). Using this unbiased approach, we show here that despite some similarities between immature and dedifferentiated β cells, β cells Dedifferentiation in the two mouse models is not a reversal of developmental ontogeny and is different between different types of diabetes.
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the anna karenina model of beta cell maturation in development and their Dedifferentiation in type 1 and type 2 diabetes
bioRxiv, 2021Co-Authors: Sutichot D Nimkulrat, Jared Brown, Christina Kendziorski, Barak BlumAbstract:Loss of mature {beta} cell function and identity, or {beta} cell Dedifferentiation, is seen in all types of diabetes mellitus. Two competing models explain {beta} cell Dedifferentiation in diabetes. In the first model, {beta} cells dedifferentiate in the reverse order of their developmental ontogeny. This model predicts that dedifferentiated {beta} cells resemble {beta} cell progenitors. In the second model, {beta} cell Dedifferentiation depends on the type of diabetogenic stress. This model, which we call the "Anna Karenina" model, predicts that in each type of diabetes, {beta} cells dedifferentiate in their own way, depending on how their mature identity is disrupted by any particular diabetogenic stress. We directly tested the two models using a {beta} cell-specific lineage-tracing system coupled with RNA-sequencing in mice. We constructed a multidimensional map of {beta} cell transcriptional trajectories during the normal course of {beta} cell postnatal development and during their Dedifferentiation in models of both type 1 diabetes (NOD) and type 2 diabetes (BTBR-Lepob/ob). Using this unbiased approach, we show here that despite some similarities between immature and dedifferentiated {beta} cells, {beta} cells Dedifferentiation in the two mouse models is not a reversal of developmental ontogeny and is different between different types of diabetes.
Bin Zhou - One of the best experts on this subject based on the ideXlab platform.
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Dedifferentiation proliferation and redifferentiation of adult mammalian cardiomyocytes after ischemic injury
Circulation, 2017Co-Authors: Wei Eric Wang, Xuewei Xia, Qiao Liao, Cong Lan, Dezhong Yang, Hongmei Chen, Rongchuan Yue, C Zeng, Lin Zhou, Bin ZhouAbstract:Background: Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACMs) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. Methods: β-Actin-green fluorescent protein transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs. In a coculture system with neonatal rat ventricular myocytes, ACM proliferation was documented with clear evidence of cytokinesis observed with time-lapse imaging. Cardiomyocyte proliferation in the adult mouse post-MI heart was detected by cell cycle markers and 5-ethynyl-2-deoxyuridine incorporation analysis. Echocardiography was used to measure cardiac function, and histology was performed to determine infarction size. Results: In vitro, mononucleated and bi/multinucleated ACMs were able to proliferate at a similar rate (7.0%) in the coculture. Dedifferentiation proceeded ACM proliferation, which was followed by redifferentiation. Redifferentiation was essential to endow the daughter cells with cardiomyocyte contractile function. Intercellular propagation of Ca 2+ from contracting neonatal rat ventricular myocytes into ACM daughter cells was required to activate the Ca 2+ -dependent calcineurin-nuclear factor of activated T-cell signaling pathway to induce ACM redifferentiation. The properties of neonatal rat ventricular myocyte Ca 2+ transients influenced the rate of ACM redifferentiation. Hypoxia impaired the function of gap junctions by dephosphorylating its component protein connexin 43, the major mediator of intercellular Ca 2+ propagation between cardiomyocytes, thereby impairing ACM redifferentiation. In vivo, ACM proliferation was found primarily in the MI border zone. An ischemia-resistant connexin 43 mutant enhanced the redifferentiation of ACM-derived new cardiomyocytes after MI and improved cardiac function. Conclusions: Mature ACMs can reenter the cell cycle and form new cardiomyocytes through a 3-step process: Dedifferentiation, proliferation, and redifferentiation. Intercellular Ca 2+ signal from neighboring functioning cardiomyocytes through gap junctions induces the redifferentiation process. This novel mechanism contributes to new cardiomyocyte formation in post-MI hearts in mammals.
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Dedifferentiation proliferation and redifferentiation of adult mammalian cardiomyocytes after ischemic injury
Circulation, 2017Co-Authors: Wei Eric Wang, Xuewei Xia, Qiao Liao, Cong Lan, Dezhong Yang, Hongmei Chen, Rongchuan Yue, C Zeng, Lin Zhou, Bin ZhouAbstract:Background:Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACMs) is a potential source of new cardiomyocytes. Understan...
Zhenhua Feng - One of the best experts on this subject based on the ideXlab platform.
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involvement of plant stem cells or stem cell like cells in Dedifferentiation
Frontiers in Plant Science, 2015Co-Authors: Fangwei Jiang, Zhenhua FengAbstract:Dedifferentiation is the transformation of cells from a given differentiated state to a less differentiated or stem cell-like state. Stem cell-related genes play important roles in Dedifferentiation, which exhibits similar histone modification and DNA methylation features to stem cell maintenance. Hence, stem cell-related factors possibly synergistically function to provide a specific niche beneficial to Dedifferentiation. During callus formation in Arabidopsis petioles, cells adjacent to procambium cells (stem cell-like cells) are dedifferentiated and survive more easily than other cell types. This finding indicates that stem cells or stem cell-like cells may influence the dedifferentiating niche. In this paper, we provide a brief overview of stem cell maintenance and Dedifferentiation regulation. We also summarize current knowledge of genetic and epigenetic mechanisms underlying the balance between differentiation and Dedifferentiation. Furthermore, we discuss the correlation of stem cells or stem cell-like cells with Dedifferentiation.
