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1.
Nat Commun ; 15(1): 1098, 2024 Feb 06.
Article En | MEDLINE | ID: mdl-38321030

In angiosperms, the transition from floral-organ maintenance to abscission determines reproductive success and seed dispersion. For petal abscission, cell-fate decisions specifically at the petal-cell base are more important than organ-level senescence or cell death in petals. However, how this transition is regulated remains unclear. Here, we identify a jasmonic acid (JA)-regulated chromatin-state switch at the base of Arabidopsis petals that directs local cell-fate determination via autophagy. During petal maintenance, co-repressors of JA signaling accumulate at the base of petals to block MYC activity, leading to lower levels of ROS. JA acts as an airborne signaling molecule transmitted from stamens to petals, accumulating primarily in petal bases to trigger chromatin remodeling. This allows MYC transcription factors to promote chromatin accessibility for downstream targets, including NAC DOMAIN-CONTAINING PROTEIN102 (ANAC102). ANAC102 accumulates specifically at the petal base prior to abscission and triggers ROS accumulation and cell death via AUTOPHAGY-RELATED GENEs induction. Developmentally induced autophagy at the petal base causes maturation, vacuolar delivery, and breakdown of autophagosomes for terminal cell differentiation. Dynamic changes in vesicles and cytoplasmic components in the vacuole occur in many plants, suggesting JA-NAC-mediated local cell-fate determination by autophagy may be conserved in angiosperms.


Arabidopsis , Cyclopentanes , Oxylipins , Arabidopsis/genetics , Flowers/genetics , Reactive Oxygen Species/metabolism , Autophagy , Chromatin/metabolism , Gene Expression Regulation, Plant
2.
J Hypertens ; 42(3): 441-449, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-37937516

OBJECTIVES: The role of hypercholesterolemia in arterial stiffness, which usually reflects the progression of atherosclerosis has not been fully investigated. To clarify the meaning of arterial stiffness in hypercholesterolemia, we evaluated arterial stiffness in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits by using new arterial stiffness indices of the aorta and common iliac to femoral artery. The new arterial stiffness indices of both arteries were determined by the application of the theory of cardio-ankle vascular index (CAVI) to the aorta (aBeta) and ilio-femoral artery (ifBeta). Furthermore, the responses of both indices to nitroglycerin (NTG) administration were compared between WHHHMI and normal rabbits. DESIGN AND METHODS: aBeta and ifBeta of WHHLMI and normal rabbits were measured under anesthesia. Pulse wave velocity in the whole aorta (aPWV) and ilio-femoral artery (ifPWV), blood pressure, and other parameters were measured before and after administration of NTG (50-120 µg/kg/min) every 1 for 5 min. RESULTS: Atherosclerotic lesions were observed in the aorta, but a little in the ilio-femoral artery in WHHLMI rabbits. Compared with normal rabbits, aBeta was significantly higher, but ifBeta was lower in WHHLMI rabbits. When NTG was administered, ifBeta decreased significantly in both groups; however, aBeta increased in normal rabbits, but remained unchanged in WHHIMI rabbits. CONCLUSION: These findings suggested that hereditary hypercholesterolemia in rabbits did not uniformly enhance arterial stiffness in elastic artery and muscular artery. The responses to NTG were also different between two arteries. The mechanism of these different responses needs further studies.


Atherosclerosis , Hypercholesterolemia , Myocardial Infarction , Vascular Stiffness , Animals , Rabbits , Nitroglycerin/pharmacology , Pulse Wave Analysis , Hypercholesterolemia/complications , Hypercholesterolemia/drug therapy , Myocardial Infarction/drug therapy , Aorta/pathology , Femoral Artery
3.
Nat Plants ; 9(11): 1862-1873, 2023 11.
Article En | MEDLINE | ID: mdl-37798337

Pre-zygotic interspecies incompatibility in angiosperms is an important mechanism to prevent unfavourable hybrids between species. Here we report our identification of STIGMATIC PRIVACY 2 (SPRI2), a transcription factor that has a zinc-finger domain and regulates interspecies barriers in Arabidopsis thaliana, via genome-wide association study. Knockout analysis of SPRI2/SRS7 and its paralogue SPRI2-like/SRS5 demonstrated their necessity in rejecting male pollen from other species within female pistils. Additionally, they govern mRNA transcription of xylan O-acetyltransferases (TBL45 and TBL40) related to cell wall modification, alongside SPRI1, a pivotal transmembrane protein for interspecific pollen rejection. SPRI2/SRS7 is localized as condensed structures in the nucleus formed via liquid-liquid phase separation (LLPS), and a prion-like sequence in its amino-terminal region was found to be responsible for the formation of the condensates. The LLPS-regulated SPRI2/SRS7 discovered in this study may contribute to the establishment of interspecific reproductive barriers through the transcriptional regulation of cell wall modification genes and SPRI1.


Arabidopsis , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Genome-Wide Association Study , Arabidopsis/genetics , Arabidopsis/metabolism , Pollen/genetics , Reproduction
4.
Int J Mol Sci ; 24(17)2023 Aug 27.
Article En | MEDLINE | ID: mdl-37686100

Heat stress (HS) is becoming an increasingly large problem for food security as global warming progresses. As sessile species, plants have evolved different mechanisms to cope with the disruption of cellular homeostasis, which can impede plant growth and development. Here, we summarize the mechanisms underlying transcriptional regulation mediated by transcription factors, epigenetic regulators, and regulatory RNAs in response to HS. Additionally, cellular activities for adaptation to HS are discussed, including maintenance of protein homeostasis through protein quality control machinery, and autophagy, as well as the regulation of ROS homeostasis via a ROS-scavenging system. Plant cells harmoniously regulate their activities to adapt to unfavorable environments. Lastly, we will discuss perspectives on future studies for improving urban agriculture by increasing crop resilience to HS.


Acclimatization , Agriculture , Reactive Oxygen Species , Autophagy , Heat-Shock Response/genetics
5.
Methods Mol Biol ; 2686: 429-451, 2023.
Article En | MEDLINE | ID: mdl-37540372

The generation of dominant gain-of-function mutants through activation tagging is a forward genetic approach that can be applied to study the mechanisms of flower development, complementing the screening of loss-of-function mutants. In addition, the functions of genes of interest can be further analyzed through reverse genetics. A commonly used method is gene overexpression, where ectopic expression can result in an opposite phenotype to that caused by a loss-of-function mutation. When overexpression is detrimental, the misexpression of a gene using tissue-specific promoters can be useful to study spatial-specific function. As flower development is a multistep process, it can be advantageous to control gene expression, or its protein product activity, in a temporal and/or spatial manner. This has been made possible through several inducible promoter systems as well as inducible proteins by constructing chimeric fusions between the ligand-binding domain of the glucocorticoid receptor (GR) and the protein of interest. The recently introduced CRISPR-Cas9-based platform provides a new way of bioengineering transcriptional regulators in plants. By fusing a catalytically inactive dCas9 with functional activation or repression domains, the CRISPR-Cas9 module can achieve transcriptional activation or repression of endogenous genes. All these methods allow us to genetically manipulate gene expression during flower development. In this chapter, we describe methods to produce the expression constructs, method of screening, and more general applications of the techniques.


CRISPR-Cas Systems , Plants , Transcriptional Activation , Phenotype , Plants/genetics , Flowers/genetics
6.
Plant Cell ; 35(8): 2821-2847, 2023 08 02.
Article En | MEDLINE | ID: mdl-37144857

The MADS domain transcription factor AGAMOUS (AG) regulates floral meristem termination by preventing maintenance of the histone modification lysine 27 of histone H3 (H3K27me3) along the KNUCKLES (KNU) coding sequence. At 2 d after AG binding, cell division has diluted the repressive mark H3K27me3, allowing activation of KNU transcription prior to floral meristem termination. However, how many other downstream genes are temporally regulated by this intrinsic epigenetic timer and what their functions are remain unknown. Here, we identify direct AG targets regulated through cell cycle-coupled H3K27me3 dilution in Arabidopsis thaliana. Expression of the targets KNU, AT HOOK MOTIF NUCLEAR LOCALIZED PROTEIN18 (AHL18), and PLATZ10 occurred later in plants with longer H3K27me3-marked regions. We established a mathematical model to predict timing of gene expression and manipulated temporal gene expression using the H3K27me3-marked del region from the KNU coding sequence. Increasing the number of del copies delayed and reduced KNU expression in a polycomb repressive complex 2- and cell cycle-dependent manner. Furthermore, AHL18 was specifically expressed in stamens and caused developmental defects when misexpressed. Finally, AHL18 bound to genes important for stamen growth. Our results suggest that AG controls the timing of expression of various target genes via cell cycle-coupled dilution of H3K27me3 for proper floral meristem termination and stamen development.


Arabidopsis Proteins , Arabidopsis , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Meristem , Histones/genetics , Histones/metabolism , Flowers/physiology , Arabidopsis/metabolism , Cell Division , Gene Expression Regulation, Plant/genetics , AGAMOUS Protein, Arabidopsis/genetics , AGAMOUS Protein, Arabidopsis/metabolism
7.
Circ J ; 87(6): 791-798, 2023 05 25.
Article En | MEDLINE | ID: mdl-36740256

BACKGROUND: The saphenous vein (SV) is used as an essential conduit in coronary artery bypass grafting (CABG), but the long-term patency of SV grafts is a crucial issue. The use of the novel "no-touch" technique of harvesting the SV together with its surrounding tissue has been reported to result in good long-term graft patency of SV grafts. We recently showed that perivascular adipose tissue (PVAT) surrounding the SV (SV-PVAT) had lower levels of metaflammation and consecutive adipose tissue remodeling than did PVAT surrounding the coronary artery. However, the difference between SV-PVAT and subcutaneous adipose tissue (SCAT) remains unclear.Methods and Results: Fat pads were sampled from 55 patients (38 men, 17 women; mean [±SD] age 71±8 years) with coronary artery disease who underwent elective CABG. Adipocyte size was significantly larger in SV-PVAT than SCAT. The extent of fibrosis was smaller in SV-PVAT than SCAT. There were no significant differences between SCAT and SV-PVAT in macrophage infiltration area, quantified by antibodies for CD68, CD11c, and CD206, or in gene expression levels of metaflammation-related markers. Expression patterns of adipocyte developmental and pattern-forming genes differed between SCAT and SV-PVAT. CONCLUSIONS: The properties of SV-PVAT are close to, but not the same as, those of SCAT, possibly resulting from inherent differences in adipocytes. SV-PVAT has healthy expansion with less fibrosis in fat than SCAT.


Adipose Tissue , Saphenous Vein , Female , Humans , Saphenous Vein/transplantation , Adipose Tissue/metabolism , Coronary Artery Bypass/methods , Subcutaneous Fat , Phenotype , Fibrosis , Vascular Patency
8.
Plant Cell Physiol ; 64(3): 284-290, 2023 Mar 15.
Article En | MEDLINE | ID: mdl-36331512

Shoot stem cells act as the source of the aboveground parts of flowering plants. A precise regulatory basis is required to ensure that plant stem cells show the right status during the stages of proliferation, senescence and cell death. Over the past few decades, the genetic circuits controlling stem cell fate, including the regulatory pathways of establishment, maintenance and differentiation, have been largely revealed. However, the morphological changes and molecular mechanisms of the final stages of stem cells, which are represented by senescence and cell death, have been less studied. The senescence and death of shoot stem cells are under the control of a complex series of pathways that integrate multiple internal and external signals. Given the crucial roles of shoot stem cells in influencing plant longevity and crop yields, researchers have attempted to uncover details of stem cell senescence and death. Recent studies indicate that stem cell activity arrest is controlled by the FRUITFULL-APETALA2 pathway and the plant hormones auxin and cytokinin, while the features of senescent and dead shoot apical stem cells have also been described, with dynamic changes in reactive oxygen species implicated in stem cell death. In this review, we highlight the recent breakthroughs that have enriched our understanding of senescence and cell death processes in plant stem cells.


Arabidopsis Proteins , Arabidopsis , Plant Senescence , Plant Shoots , Stem Cells , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cytokinins/genetics , Cytokinins/metabolism , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Meristem/genetics , Meristem/metabolism , Plant Growth Regulators/genetics , Plant Growth Regulators/metabolism , Plant Senescence/genetics , Plant Senescence/physiology , Plant Shoots/genetics , Plant Shoots/metabolism , Plant Shoots/physiology , Regulated Cell Death/genetics , Regulated Cell Death/physiology , Stem Cells/metabolism , Stem Cells/physiology
9.
Plant Cell Physiol ; 64(2): 234-247, 2023 Mar 01.
Article En | MEDLINE | ID: mdl-36440710

The glucosinolate-myrosinase defense system (GMDS), characteristic of Brassicales, is involved in plant defense. Previous single-cell transcriptomic analyses have reported the expression profiles of multiple GMDS-related cell types (i.e. myrosinase-rich myrosin idioblasts and multiple types of potential glucosinolate synthetic cells as well as a candidate S-cell for glucosinolate accumulation). However, differences in plant stages and cell-type annotation methods have hindered comparisons among studies. Here, we used the single-cell transcriptome profiles of extended Arabidopsis leaves and verified the distribution of previously used markers to refine the expression profiles of GMDS-associated cell types. Moreover, we performed beta-glucuronidase promoter assays to confirm the histological expression patterns of newly obtained markers for GMDS-associated candidates. As a result, we found a set of new specific reporters for myrosin cells and potential glucosinolate-producing cells.


Arabidopsis , Arabidopsis/genetics , Glucosinolates/metabolism , Plant Leaves/metabolism , Glycoside Hydrolases/metabolism , Glucuronidase/metabolism , Plants/metabolism , Sequence Analysis, RNA
10.
Transpl Immunol ; 75: 101713, 2022 12.
Article En | MEDLINE | ID: mdl-36100196

Vaccination against SARS-COV-2 is considered the most promising approach to curbing the pandemic. Patients with an immunocompromised state, such as those with hematological malignancies and organ transplantation recipients, are considered more susceptible to infection, but these at-risk patients were underrepresented in early clinical trials for vaccination. Although a growing body of studies suggests that the humoral response to COVID-19 vaccination in each of these at-risk groups of patients may be suboptimal in comparison to healthy controls, a clinical and strategic information for the further comparative analysis among these groups is not fully described. The humoral responses after two doses of BNT162b2 vaccination were evaluated in a total of 187 patients either with allogeneic hematopoietic transplantation, with renal transplantation, with anti-CD20 antibody therapy, or with anti-CD38 antibody therapy, and in 66 healthy controls. The early response at one to three months after vaccination was significantly inferior among patients with renal transplantation, patients with anti-CD20 antibody therapy, and patients with anti-CD38 antibody therapy in comparison to healthy control. But the patients with allogeneic hematopoietic transplantation showed early humoral response comparable to healthy control. The late response at 6 months after vaccination was still suboptimal among patients with renal transplantation and patients with anti-CD20 therapy. Among our patient group, renal transplant recipients had the lowest antibody titers after vaccination regardless of timing of vaccination. Patients who had received allogeneic hematopoietic transplantation attained a comparable serological response to the control group especially if they are vaccinated >300 days after transplantation, but the response was suboptimal if the vaccination was within 300 days after transplantation. Our results may provide policy makers with critical information for the further stratification of at-risk groups, helping contribute to a better allocation of resources, including additional booster vaccination.


COVID-19 , Influenza Vaccines , Organ Transplantation , Humans , BNT162 Vaccine , COVID-19 Vaccines/therapeutic use , Antibodies, Viral , SARS-CoV-2 , COVID-19/prevention & control , Transplant Recipients
11.
Front Plant Sci ; 13: 837831, 2022.
Article En | MEDLINE | ID: mdl-35845667

Vernalization is the promotion of flowering after prolonged exposure to cold. In Arabidopsis thaliana, vernalization induces epigenetic silencing of the floral repressor gene FLOWERING LOCUS C (FLC). Among the repressive epigenetic marks, the trimethylation of lysine 27 on histone H3 proteins (H3K27me3) is a critical contributor to the epigenetic silencing of FLC. The deposition of H3K27me3 is mediated by Polycomb Repressive Complex 2 (PRC2). Conversely, the elimination of H3K27me3 is mediated by histone demethylases, Jumonji-C domain-containing protein JMJ30 and its homolog JMJ32. However, the role of JMJ30 and JMJ32 in vernalization is largely unknown. In this study, we found that cold treatment dramatically reduced the expression levels of JMJ30 and did not reduce those of JMJ32. Next, by using the genetic approach, we found that the flowering of jmj30 jmj32 was accelerated under moderate vernalized conditions. Under moderate vernalized conditions, the silencing of FLC occurred more quickly in jmj30 jmj32 than in the wild type. These results suggested that the histone demethylases JMJ30 and JMJ32 brake vernalization through the activation of FLC. Our study suggested that PRC2 and Jumonji histone demethylases act in an opposing manner to regulate flowering time via epigenetic modifications.

12.
Asian Cardiovasc Thorac Ann ; 30(7): 797-806, 2022 Sep.
Article En | MEDLINE | ID: mdl-35603636

BACKGROUND: There are increasing reports of early externally mounted pericardial Trifecta bioprosthesis failure. We compared the hemodynamic performance of Trifecta and Carpentier-Edwards Perimount Magna Ease valves to determine the failure mechanism. METHODS: We retrospectively included 270 consecutive patients (age: 73.4 ± 8.2 years; 57.5% male; mean follow-up: 48.0 ± 20.3 months) who underwent aortic valve replacement from 2014 to 2021 at a single center and compared the Trifecta (N = 137) and Carpentier-Edwards Perimount Magna Ease valve (N = 133) patients. RESULTS: The prosthetic valve major aortic regurgitation incidence was higher for the Trifecta than that for the Carpentier-Edwards Perimount Magna Ease valve (6.3% vs. 0%, P < 0.009). Among the Trifecta failures, 33% developed structural valve deterioration, but all requiring redo aortic valve replacement developed major prosthetic valve aortic regurgitation. Freedom at 5 years from redo aortic valve replacement due to structural valve deterioration was significantly lower for Trifecta (89.4% vs. 100%, P = 0.003). The reoperation hazards were determined for Trifecta (vs. Carpentier-Edwards Perimount Magna Ease): 11.6 (1.47-90.9; P = 0.02), prosthetic valve aortic regurgitation: 2.38 (1.70-3.32; P < 0.01), structural valve deterioration: 20.82 (4.08-106.2; P < 0.01), 5-year mean transprosthetic pressure gradient: 1.14 per 1-point increase (1.03-1.24; P = 0.007), and urgent surgery: 10.1 (2.59-39.0; P = 0.001). The Cox regression analysis identified that prosthetic valve aortic regurgitation solely contributed to redo aortic valve replacement (hazard ratio: 2.38; confidence intervals: 1.70-3.32). CONCLUSIONS: Significantly, more early failures occurred with the Trifecta valve than the Carpentier-Edwards Perimount Magna Ease valve but the Trifecta showed reasonable mean transprosthetic pressure gradient over time. Prosthetic valve aortic regurgitation and calcific structural valve deterioration synergistically contributed to Trifecta valve failure alternatively.


Aortic Valve Insufficiency , Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/etiology , Aortic Valve Insufficiency/surgery , Female , Heart Valve Prosthesis Implantation/adverse effects , Hemodynamics , Humans , Male , Prosthesis Design , Retrospective Studies , Treatment Outcome
13.
BMC Plant Biol ; 22(1): 248, 2022 May 19.
Article En | MEDLINE | ID: mdl-35590269

BACKGROUND: Leaf senescence, the final stage of leaf growth and development, is regulated by numerous internal factors and environmental cues. Ethylene is one of the key senescence related hormones, but the underlying molecular mechanism of ethylene-induced leaf senescence remains poorly understood. RESULTS: In this study, we identified one AT-hook like (AHL) protein, AHL9, as a positive regulator of leaf senescence in Arabidopsis thaliana. Overexpression of AHL9 significantly accelerates age-related leaf senescence and promotes dark-induced leaf chlorosis. The early senescence phenotype observed in AHL9 overexpressing lines is inhibited by the ethylene biosynthesis inhibitor aminooxyacetic acid suggesting the involvement of ethylene in the AHL9-associated senescence. RNA-seq and quantitative reverse transcription PCR (qRT-PCR) data identified numerous senescence-associated genes differentially expressed in leaves of AHL9 overexpressing transgenic plants. CONCLUSIONS: Our investigation demonstrates that AHL9 functions in accelerating the leaf senescence process via ethylene synthesis or signalling.


Arabidopsis Proteins , Arabidopsis , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Ethylenes/metabolism , Gene Expression Regulation, Plant , Plant Leaves/genetics , Plant Leaves/metabolism , Plant Senescence , Plants, Genetically Modified/metabolism , Transcription Factors/genetics
14.
Int J Mol Sci ; 23(7)2022 Mar 31.
Article En | MEDLINE | ID: mdl-35409227

In monocarpic plants, stem cells are fated to die. However, the potential mechanism of stem cell death has remained elusive. Here, we reveal that the levels of two forms of reactive oxygen species (ROS), superoxide anion free radical (O2·-) and hydrogen peroxide (H2O2), show dynamic changes in the shoot apex during the plant life cycle of Arabidopsis thaliana. We found that the level of O2·- decreased and disappeared at four weeks after bolting (WAB), while H2O2 appeared at 3 WAB and showed a burst at 5 WAB. The timing of dynamic changes in O2·- and H2O2 was delayed for approximately three weeks in clv3-2, which has a longer lifespan. Moreover, exogenous application of H2O2 inhibited the expression of the stem cell determinant WUSCHEL (WUS) and promoted the expression of the developmentally programmed cell death (dPCD) marker gene ORESARA 1 (ORE1). These results indicate that H2O2 triggers an important signal inducing dPCD in stem cells. Given that O2·- plays roles in maintaining WUS expression and stem cell activity, we speculate that the dynamic shift from O2·- to H2O2 in the shoot apex results in stem cell death. Our findings provide novel insights for understanding ROS-mediated regulation during plant stem cell death.


Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cell Death , Gene Expression Regulation, Plant , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , Reactive Oxygen Species/metabolism , Stem Cells/metabolism
15.
J Surg Case Rep ; 2022(3): rjac099, 2022 Mar.
Article En | MEDLINE | ID: mdl-35350214

Transcatheter aortic valve replacement (TAVR) is the treatment of choice for aortic stenosis. However, its safety and efficacy in patients with the bicuspid aortic valve (BAV) remain controversial. Especially, whether the BAV phenotype affects outcomes following TAVR remains debated. Despite the higher ellipticity index and more calcifications of the aortic annulus in type 1 BAV, a high residual gradient was observed in type 0 anatomy. Moreover, severe calcification of the cusps rather than aortic annulus in type 0 is predisposed to asymmetrical under-expansion of the prosthesis at the edge of the native aortic cusp. We report the rare case of a patient with BAV stenosis type 0 and single coronary artery receiving TAVR, subsequently requiring surgical aortic valve replacement. The extensive non-coronary cusp calcification caused under-expansion of the prosthesis and was protruded into the left ventricular outflow tract, leading to an obstruction.

16.
Blood Adv ; 6(2): 624-636, 2022 01 25.
Article En | MEDLINE | ID: mdl-34516628

The standard treatment for adults with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in Japan is imatinib-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, ∼40% of patients cannot undergo HSCT in their first complete remission (CR1) because of chemotherapy-related toxicities or relapse before HSCT or older age. In this study, we evaluated dasatinib-based 2-step induction with the primary end point of 3-year event-free survival (EFS). The first induction (IND1) was dasatinib plus prednisolone to achieve CR, and IND2 was dasatinib plus intensive chemotherapy to achieve minimal residual disease (MRD) negativity. For patients who achieved CR and had an appropriate donor, HSCT during a consolidation phase later than the first consolidation, which included high-dose methotrexate, was recommended. Patients with pretransplantation MRD positivity were assigned to receive prophylactic dasatinib after HSCT. All 78 eligible patients achieved CR or incomplete CR after IND1, and 52.6% achieved MRD negativity after IND2. Nonrelapse mortality (NRM) was not reported. T315I mutation was detected in all 4 hematological relapses before HSCT. Fifty-eight patients (74.4%) underwent HSCT in CR1, and 44 (75.9%) had negative pretransplantation MRD. At a median follow-up of 4.0 years, 3-year EFS and overall survival were 66.2% (95% confidence interval [CI], 54.4-75.5) and 80.5% (95% CI, 69.7-87.7), respectively. The cumulative incidence of relapse and NRM at 3 years from enrollment were 26.1% and 7.8%, respectively. Dasatinib-based 2-step induction was demonstrated to improve 3-year EFS in Ph+ ALL. This study was registered in the UMIN Clinical Trial Registry as #UMIN000012173.


Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Acute Disease , Adult , Dasatinib/therapeutic use , Humans , Imatinib Mesylate , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Recurrence
17.
Proc Natl Acad Sci U S A ; 118(36)2021 09 07.
Article En | MEDLINE | ID: mdl-34462349

Floral organs are properly developed on the basis of timed floral meristem (FM) termination in Arabidopsis In this process, two known regulatory pathways are involved. The WUSCHEL (WUS)-CLAVATA3 (CLV3) feedback loop is vital for the spatial establishment and maintenance of the FM, while AGAMOUS (AG)-WUS transcriptional cascades temporally repress FM. At stage 6 of flower development, a C2H2-type zinc finger repressor that is a target of AG, KNUCKLES (KNU), directly represses the stem cell identity gene WUS in the organizing center for FM termination. However, how the robust FM activity is fully quenched within a limited time frame to secure carpel development is not fully understood. Here, we demonstrate that KNU directly binds to the CLV1 locus and the cis-regulatory element on CLV3 promoter and represses their expression during FM determinacy control. Furthermore, KNU physically interacts with WUS, and this interaction inhibits WUS from sustaining CLV3 in the central zone. The KNU-WUS interaction also interrupts the formation of WUS homodimers and WUS-HAIRYMERISTEM 1 heterodimers, both of which are required for FM maintenance. Overall, our findings describe a regulatory framework in which KNU plays a position-specific multifunctional role for the tightly controlled FM determinacy.


Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Carrier Proteins/metabolism , Flowers/metabolism , Meristem/metabolism , Flowers/cytology , Homeodomain Proteins/metabolism , Protein Binding , Repressor Proteins/metabolism , Signal Transduction , Stem Cells/metabolism
18.
Biomolecules ; 11(6)2021 06 07.
Article En | MEDLINE | ID: mdl-34200465

Exposure to moderately high temperature enables plants to acquire thermotolerance to high temperatures that might otherwise be lethal. In Arabidopsis thaliana, histone H3 lysine 27 trimethylation (H3K27me3) at the heat shock protein 17.6C (HSP17.6C) and HSP22 loci is removed by Jumonji C domain-containing protein (JMJ) histone demethylases, thus allowing the plant to 'remember' the heat experience. Other heat memory genes, such as HSP21, are downregulated in acclimatized jmj quadruple mutants compared to the wild type, but how those genes are regulated remains uncharacterized. Here, we show that histone H3 lysine 4 trimethylation (H3K4me3) at HSP21 was maintained at high levels for at least three days in response to heat. This heat-dependent H3K4me3 accumulation was compromised in the acclimatized jmj quadruple mutant as compared to the acclimatized wild type. JMJ30 directly bound to the HSP21 locus in response to heat and coordinated H3K27me3 and H3K4me3 levels under standard and fluctuating conditions. Our results suggest that JMJs mediate the balance between H3K27me3 and H3K4me3 at the HSP21 locus through proper maintenance of H3K27me3 removal during heat acclimation.


Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Genetic Loci/physiology , Heat-Shock Proteins/metabolism , Histones/metabolism , Thermotolerance/physiology , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Heat-Shock Proteins/genetics , Histones/genetics , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism
19.
Int J Mol Sci ; 22(13)2021 Jun 29.
Article En | MEDLINE | ID: mdl-34209661

Self-incompatibility (SI) is conserved among members of the Brassicaceae plant family. This trait is controlled epigenetically by the dominance hierarchy of the male determinant alleles. We previously demonstrated that a single small RNA (sRNA) gene is sufficient to control the linear dominance hierarchy in Brassica rapa and proposed a model in which a homology-based interaction between sRNAs and target sites controls the complicated dominance hierarchy of male SI determinants. In Arabidopsis halleri, male dominance hierarchy is reported to have arisen from multiple networks of sRNA target gains and losses. Despite these findings, it remains unknown whether the molecular mechanism underlying the dominance hierarchy is conserved among Brassicaceae. Here, we identified sRNAs and their target sites that can explain the linear dominance hierarchy of Arabidopsis lyrata, a species closely related to A. halleri. We tested the model that we established in Brassica to explain the linear dominance hierarchy in A. lyrata. Our results suggest that the dominance hierarchy of A. lyrata is also controlled by a homology-based interaction between sRNAs and their targets.


Arabidopsis/genetics , Epistasis, Genetic , Gene Expression Regulation, Plant , Genes, Dominant , Homologous Recombination , RNA, Plant , Social Dominance , Alleles , Genotype , Haplotypes , Nucleic Acid Conformation
20.
Plant Signal Behav ; 16(11): 1950445, 2021 11 02.
Article En | MEDLINE | ID: mdl-34227901

Histone modification influences gene expression. Among histone modifications, H3K27me3 is associated with downregulation of nearby genes via chromatin compaction. In Arabidopsis thaliana, a subset of JUMONJI C DOMAIN-CONTAINING PROTEIN (JMJ) proteins play a critical role in removal of H3K27me3 during plant development or in response to environmental cues. However, the regulation of H3K27me3 demethylase gene expression is not yet fully characterized. In this study, we computationally characterized the expression patterns of JMJ H3K27me3 demethylase genes using public transcriptome datasets created across plant development and after various environmental cues. Consistent with the available transcriptome datasets, GUS staining validated that JMJ30 was highly expressed in the L1 layer of the shoot apical meristem. Furthermore, expression data for panel of five H3K27me3 demethylase genes revealed JMJ30 to be the most highly affected by abiotic and biotic stress. In addition, JMJ30 expression was variable between Arabidopsis thaliana accessions. Finally, the expression of a JMJ30 orthologue from the related species Arabidopsis halleri, AhgJMJ30, fluctuated under field conditions. Taken together, our results suggest that transcriptional changes of H3K27me3 demethylase genes may play key roles in development and environmental responses.


Adaptation, Physiological/genetics , Arabidopsis/growth & development , Arabidopsis/genetics , Histone Demethylases/genetics , Histone Demethylases/metabolism , Plant Development/genetics , Plant Development/physiology , Arabidopsis/metabolism , Gene Expression Regulation, Plant , Genes, Plant , Stress, Physiological/physiology
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