scholarly journals Genome-wide Analysis of the WUSCHEL-related Homeobox Gene Family and Functional Characterization of VcWOX4b Regarding the Inhibition of Adventitious Root Formation in Blueberry (Vaccinium Spp.)

2021 ◽  
Author(s):  
Yudi Gao ◽  
Ke Li ◽  
Yahong Yin ◽  
Yongqiang Li ◽  
Yu Zong ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Cell Differentiation ◽  
Molecular Mechanisms ◽  
Secondary Xylem ◽  
Functional Characterization ◽  
Vaccinium Corymbosum ◽  
Dependent Manner ◽  
High Quality ◽  
Primary Xylem ◽  
Xylem Cell

Abstract Background: Blueberry (Vaccinium corymbosum L.) is one of the most important commercial fruit tree species. The development of high-quality seedlings is a prerequisite for fruit production. Stem cutting and tissue culture methods are widely applied for propagating blueberry seedlings. Both methods require adventitious roots (ARs), indicating ARs are critical for vegetative propagation. However, the underlying factors and molecular mechanisms regulating blueberry AR formation remain relatively unknown. Results: In this study, the rooting abilities of differentially lignified cuttings from various cultivars or the same cultivars cultured differently were evaluated following an indole-3-butyric acid (IBA) treatment. Field-grown semi-lignified and tissue culture-grown cuttings formed ARs, but the latter had more pericycle and secondary xylem cells and formed ARs more easily and faster. WUSCHEL-related homeobox genes are commonly involved in vascular tissue development and early root meristem maintenance. On the basis of the available Vaccinium corymbosum genome data, 29 putative WOX genes with conserved homeodomains were identified and divided into three major clades (modern/WUS, intermediate, and ancient). These 29 WOX genes were differentially expressed in the root, shoot, leaf, flower bud, and fruit. Additionally, a qRT-PCR analysis revealed that five selected VcWOX genes were responsive to an IBA treatment during AR formation. Accordingly, VcWOX4b was functionally characterized. The overexpression of VcWOX4b in transgenic tobacco inhibited AR formation by altering vascular cell division and differentiation and the indole-3-acetic acid (IAA):cytokinin (CTK) ratio. These observations suggest that VcWOX4b regulates the IAA:CTK ratio to promote primary xylem cell differentiation, thereby inhibiting AR formation. However, an IBA treatment can induce AR formation by inhibiting VcWOX4b expression. Conclusions: Current study elucidates the rooting abilities of various cultivars and the cytological characters of influence on AR formation of blueberry cuttings, which may provide novel insights into the selection of high-quality blueberry cuttings. VcWOX4b, VcWOX8/9a, VcWOX11/12c, and VcWOX13b might regulate blueberry AR formation in an IBA-dependent manner. Ectopic expression of VcWOX4b modulated the IAA:CTK ratio to promotes primary xylem cell differentiation, but inhibit secondary xylem cell differentiation, ultimately leading to decreased AR formation.

scholarly journals Molecular Mechanisms Driving Bistable Switch Behavior in Xylem Cell Differentiation

2019 ◽  
Author(s):  
Gina M Turco ◽  
Joel Rodriguez-Medina ◽  
Stefan Siebert ◽  
Diane Han ◽  
Hannah Vahldick ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Molecular Mechanisms ◽  
Terminal Differentiation ◽  
Emergent Properties ◽  
Bistable Switch ◽  
Xylem Cell ◽  
Binary Switch ◽  
Regulatory Architecture ◽  
Bistable Switching ◽  
Cell Data

SummaryPlant xylem cells conduct water and mineral nutrients. Although most plant cells are totipotent, xylem cells are unusual and undergo terminal differentiation. Many genes regulating this process are well characterized, including the VASCULAR-RELATED NAC DOMAIN7 (VND7), MYB46 and MYB83 transcription factors which are proposed to act in interconnected feed-forward loops. Much less is known regarding the dynamic behavior underlying the terminal transition to xylem cell differentiation. Here we utilize whole root and single cell data to mathematically model this relationship. These provide evidence for VND7 regulating bistable switching of cells in the root to a xylem cell identity, with additional features of hysteresis. We further determine that although MYB46 responds to VND7 induction, it is not inherently involved in executing the binary switch. A novel regulatory architecture is proposed that involves four downstream targets of VND7 that act in a cycle. These data provide an important model to study the emergent properties that may give rise to totipotency relative to terminal differentiation and reveal novel xylem cell subtypes.

scholarly journals Investigating the Role of Guanosine on Human Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Natale Belluardo ◽  
Giuseppa Mudò ◽  
Valentina Di Liberto ◽  
Monica Frinchi ◽  
Daniele F. Condorelli ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Molecular Mechanisms ◽  
Neuroblastoma Cell ◽  
Neural Crest Cell ◽  
Receptor Activation ◽  
Purine Nucleoside ◽  
Heme Oxygenase 1 ◽  
Human Neuroblastoma Cell ◽  
Dependent Manner ◽  
Human Neuroblastoma

Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. We found that GUO, added to the cell culture medium, promoted neuron-like cell differentiation in a time- and concentration-dependent manner. This effect was mainly due to an extracellular GUO action since nucleoside transporter inhibitors reduced but not abolished it. Importantly, GUO-mediated neuron-like cell differentiation was independent of adenosine receptor activation as it was not altered by the blockade of these receptors. Noteworthy, the neuritogenic activity of GUO was not affected by blocking the phosphoinositide 3-kinase pathway, while it was reduced by inhibitors of protein kinase C or soluble guanylate cyclase. Furthermore, the inhibitor of the enzyme heme oxygenase-1 but not that of nitric oxide synthase reduced GUO-induced neurite outgrowth. Interestingly, we found that GUO was largely metabolized into guanine by the purine nucleoside phosphorylase (PNP) enzyme released from cells. Taken together, our results suggest that GUO, promoting neuroblastoma cell differentiation, may represent a potential therapeutic agent; however, due to its spontaneous extracellular metabolism, the role played by the GUO-PNP-guanine system needs to be further investigated.

scholarly journals IκB Kinase-Dependent Chronic Activation of NF-κB Is Necessary for p21WAF1/Cip1 Inhibition of Differentiation-Induced Apoptosis of Monocytes

2001 ◽  
Vol 21 (6) ◽  
pp. 1930-1941 ◽  
Author(s):  
Kevin N. Pennington ◽  
Julie A. Taylor ◽  
Gary D. Bren ◽  
Carlos V. Paya
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Dependent Manner ◽  
Macrophage Differentiation ◽  
Monocyte Differentiation ◽  
Cell Functions ◽  
Iκb Kinase ◽  
Induced Apoptosis

ABSTRACT The molecular mechanisms regulating monocyte differentiation to macrophages remain unknown. Although the transcription factor NF-κB participates in multiple cell functions, its role in cell differentiation is ill defined. Since differentiated macrophages, in contrast to cycling monocytes, contain significant levels of NF-κB in the nuclei, we questioned whether this transcription factor is involved in macrophage differentiation. Phorbol 12-myristate 13-acetate (PMA)-induced differentiation of the promonocytic cell line U937 leads to persistent NF-κB nuclear translocation. We demonstrate here that an increased and persistent IKK activity correlates with monocyte differentiation leading to persistent NF-κB activation secondary to increased IκBα degradation via the IκB signal response domain (SRD). Promonocytic cells stably overexpressing an IκBα transgene containing SRD mutations fail to activate NF-κB and subsequently fail to survive the PMA-induced macrophage differentiation program. The differentiation-induced apoptosis was found to be dependent on tumor necrosis factor alpha. The protective effect of NF-κB is mediated through p21WAF1/Cip1, since this protein was found to be regulated in an NF-κB-dependent manner and to confer survival features during macrophage differentiation. Therefore, NF-κB plays a key role in cell differentiation by conferring cell survival that in the case of macrophages is mediated through p21WAF1/Cip1.

scholarly journals Interleukin 25 promotes the initiation of proallergic type 2 responses

2007 ◽  
Vol 204 (7) ◽  
pp. 1509-1517 ◽  
Author(s):  
Pornpimon Angkasekwinai ◽  
Heon Park ◽  
Yui-Hsi Wang ◽  
Yi-Hong Wang ◽  
Seon Hee Chang ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell Activation ◽  
Molecular Mechanisms ◽  
Parasitic Infection ◽  
Lung Epithelial Cells ◽  
Cell Mediated Immunity ◽  
Dependent Manner ◽  
Th2 Cell

The molecular mechanisms underlying the initiation of innate and adaptive proallergic type 2 responses are not understood. Interleukin (IL) 25, a member of the IL-17 cytokine family, was recently reported (Owyang, A.M., C. Zaph, E.H. Wilson, K.J. Guild, T. McClanahan, H.R. Miller, D.J. Cua, M. Goldschmidt, C.A. Hunter, R.A. Kastelein, and D. Artis. 2006. J. Exp. Med. 203:843–849; Fallon, P.G., S.J. Ballantyne, N.E. Mangan, J.L. Barlow, A. Dasvarma, D.R. Hewett, A. McIlgorm, H.E. Jolin, and A.N. McKenzie. 2006. J. Exp. Med. 203:1105–1116) to be important in Th2 cell–mediated immunity to parasitic infection. However, the cellular source and targets of IL-25 are not well understood. We show that mouse IL-25 is expressed by lung epithelial cells as a result of innate immune responses to allergens. Transgenic overexpression of IL-25 by these cells leads to mucus production and airway infiltration of macrophages and eosinophils, whereas blockade of IL-25 conversely reduces the airway inflammation and Th2 cytokine production in an allergen-induced asthma model. In addition, IL-25, with a receptor more highly expressed in Th2 than other effector T cells, promotes Th2 cell differentiation in an IL-4– and signal transducer and activator of transcription 6–dependent manner. During early T cell activation, IL-25 potentiates expression of the nuclear factor of activated T cells c1 and JunB transcription factors, which possibly results in increased levels of initial IL-4 production, up-regulation of GATA-3 expression, and enhanced Th2 cell differentiation. Thus, IL-25 is a critical factor regulating the initiation of innate and adaptive proallergic responses.

scholarly journals Molecular Mechanisms Driving Switch Behavior in Xylem Cell Differentiation

Cell Reports ◽  
2019 ◽  
Vol 28 (2) ◽  
pp. 342-351.e4 ◽  
Author(s):  
Gina M. Turco ◽  
Joel Rodriguez-Medina ◽  
Stefan Siebert ◽  
Diane Han ◽  
Miguel Á. Valderrama-Gómez ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Molecular Mechanisms ◽  
Xylem Cell

Differential context-dependent effects of friend of GATA-1 (FOG-1) on mast-cell development and differentiation

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1924-1932 ◽  
Author(s):  
Daijiro Sugiyama ◽  
Makoto Tanaka ◽  
Kenji Kitajima ◽  
Jie Zheng ◽  
Hilo Yen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mast Cell ◽  
Cell Differentiation ◽  
Mast Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Experimental System ◽  
Cell Phenotype ◽  
Dependent Manner

Friend of GATA-1 (FOG-1) is a binding partner of GATA-1, a zinc finger transcription factor with crucial roles in erythroid, megakaryocytic, and mast-cell differentiation. FOG-1 is indispensable for the function of GATA-1 during erythro/megakaryopoiesis, but FOG-1 is not expressed in mast cells. Here, we analyzed the role of FOG-1 in mast-cell differentiation using a combined experimental system with conditional gene expression and in vitro hematopoietic induction of mouse embryonic stem cells. Expression of FOG-1 during the progenitor period inhibited the differentiation of mast cells and enhanced the differentiation of neutrophils. Analysis using a mutant of PU.1, a transcription factor that positively or negatively cooperates with GATA-1, revealed that this lineage skewing was caused by disrupted binding between GATA-1 and PU.1, which is a prerequisite for mast-cell differentiation. However, FOG-1 expression in mature mast cells brought approximately a reversible loss of the mast-cell phenotype. In contrast to the lineage skewing, the loss of the mast-cell phenotype was caused by down-regulation of MITF, a basic helix-loop-helix transcription factor required for mast-cell differentiation and maturation. These results indicate that FOG-1 inhibits mast-cell differentiation in a differentiation stage-dependent manner, and its effects are produced via different molecular mechanisms.

scholarly journals The Winged-Helix Protein Brain Factor 1 Interacts with Groucho and Hes Proteins To Repress Transcription

2001 ◽  
Vol 21 (6) ◽  
pp. 1962-1972 ◽  
Author(s):  
Jing Yao ◽  
Eseng Lai ◽  
Stefano Stifani
Keyword(s):  
Cell Differentiation ◽  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Trichostatin A ◽  
Specific Interaction ◽  
Dependent Manner ◽  
Winged Helix ◽  
Brain Factor

ABSTRACT Brain factor 1 (BF-1) is a winged-helix transcriptional repressor that plays important roles in both progenitor cell differentiation and regional patterning in the mammalian telencephalon. The aim of this study was to elucidate the molecular mechanisms underlying BF-1 functions. It is shown here that BF-1 interacts in vivo with global transcriptional corepressors of the Groucho family and also associates with the histone deacetylase 1 protein. The ability of BF-1 to mediate transcriptional repression is promoted by Groucho and inhibited by the histone deacetylase inhibitor trichostatin A, suggesting that BF-1 recruits Groucho and histone deacetylase activities to repress transcription. Our studies also provide the first demonstration that Groucho mediates a specific interaction between BF-1 and the basic helix-loop-helix protein Hes1 and that BF-1 potentiates transcriptional repression by Hes1 in a Groucho-dependent manner. These findings suggest that Groucho participates in the transcriptional functions of BF-1 by acting as both a corepressor and an adapter between BF-1 and Hes1. Taken together with the demonstration that these proteins are coexpressed in telencephalic neural progenitor cells, these results also suggest that complexes of BF-1, Groucho, and Hes factors may be involved in the regulation of progenitor cell differentiation in the telencephalon.

scholarly journals CBIO-25. INTEGRATED MOLECULAR AND BH3 PROFILING OF THE INTRINSIC APOPTOTIC MACHINERY IDENTIFIES THERAPEUTIC VULNERABILITIES IN GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii21-ii21
Author(s):  
Elizabeth Fernandez ◽  
Wilson Mai ◽  
Nicholas Bayley ◽  
Christopher Tse ◽  
Linda Liau ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Standard Of Care ◽  
Molecular Data ◽  
Dependent Manner ◽  
Intrinsic Apoptosis ◽  
Apoptosis Resistance ◽  
Molecular Features ◽  
P53 Signaling

Abstract Resistance to apoptosis is a hallmark of cancer. However, the underlying molecular mechanisms of intrinsic-apoptotic resistance in glioblastoma (GBM) are largely unknown. Here we performed integrated molecular and functional characterization (via BH3 profiling) of the intrinsic apoptotic machinery in 50 GBM patient specimens. We found that, despite significant genetic heterogeneity of our GBM samples, all GBMs have a cross compensatory reliance on BCLXL and MCL1 for basal survival. Treatment with standard of care (e.g., temozolomide or radiation) caused minimal apoptosis, yet ablated the MCL-1 block in a p53-dependent manner, thus creating an exclusive dependence on BCLXL for survival in p53 wild-type GBM tumors (65% of GBM tumors). Consequently, BCLXL inhibition caused synergistic cell death with IR/TMZ in GBM tumors with intact p53 signaling. Importantly, the degree of synergistic cell kill was best predicted by combining molecular features with BH3 profiling, providing an integrated predictive signature of response to this novel therapeutic approach. Collectively, these studies identify mechanisms of intrinsic apoptosis resistance in both basal and treatment states of GBM and demonstrate how functional and molecular data can be complementary to robustly predict therapy-induced cell death.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

Neuroblastoma: An Updated Review on Biology and Treatment

2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Mycn Amplification ◽  
Dependent Manner ◽  
High Risk Patients ◽  
Treatment And Prevention ◽  
Risk Patients

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

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