DEVELOPMENT
·
2023
·Vol. 150
·期 10
·
IF 4.6
Zheng Huiwen,Zhang Xiaobo,Fu Jing,Xue Yifan,Chen Zhi,Yang Guobin,Chen YiPing,Chen Di,Yuan Guohua
Dentin is the major hard tissue of teeth formed by differentiated odontoblasts. How odontoblast differentiation is regulated remains enigmatic. Here, we report that the E3 ubiquitin ligase CHIP is highly expressed in undifferentiated dental mesenchymal cells and downregulated after differentiation of odontoblasts. Ectopic expression of CHIP inhibits odontoblastic differentiation of mouse dental papilla cells, whereas knockdown of endogenous CHIP has opposite effects. Chip ( Stub1 ) knockout mice display increased formation of dentin and enhanced expression of odontoblast differentiation markers. Mechanistically, CHIP interacts with and induces K63 polyubiquitylation of the transcription factor DLX3, leading to its proteasomal degradation. Knockdown of DLX3 reverses the enhanced odontoblastic differentiation caused by knockdown of CHIP. These results suggest that CHIP inhibits odontoblast differentiation by targeting its tooth-specific substrate DLX3. Furthermore, our results indicate that CHIP competes with another E3 ubiquitin ligase, MDM2, that promotes odontoblast differentiation by monoubiquitylating DLX3. Our findings suggest that the two E3 ubiquitin ligases CHIP and MDM2 reciprocally regulate DLX3 activity by catalyzing distinct types of ubiquitylation, and reveal an important mechanism by which differentiation of odontoblasts is delicately regulated by divergent post-translational modifications.
研究领域:
分子生物学
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发育生物学
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牙科科学
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DOI
PubMed
高影响因子
Foods
·
2023
·Vol. 12
·期 12
·2357
·
IF 5.2
Yanan He,Qiong Wu,Chunxiao Cui,Qisheng Tian,Dongdong Zhang,Yurong Zhang
SlAREB1, a member of the abscisic acid (ABA) response element-binding factors (AREB/ABFs) family, was reported to play a crucial role in the expression of ABA-regulated downstream genes and affect the ripening of tomato fruit. However, the downstream genes ofSlAREB1are still unclear. Chromatin immunoprecipitation (ChIP) is a powerful tool and a standard method for studying the interactions between DNA and proteins at the genome-wide level. In the present study,SlAREB1was proved to continually increase until the mature green stage and then decrease during the ripening period, and a total of 972 gene peaks were identified downstream ofSlAREB1by ChIP-seq analysis, mainly located in the intergenic and promoter regions. Further gene ontology (GO) annotation analysis revealed that the target sequence ofSlAREB1was the most involved in biological function. Kyoto Encylopaedia of Genes and Genomes (KEGG) pathway analysis showed that the identified genes were mainly involved in the oxidative phosphorylation and photosynthesis pathways, and some of them were associated with tomato phytohormone synthesis, the cell wall, pigment, and the antioxidant characteristic of the fruit as well. Based on these results, an initial model ofSlAREB1regulation on tomato fruit ripening was constructed, which provided a theoretical basis for further exploring the effects of the regulation mechanism ofSlAREB1and ABA on tomato fruit ripening.Keywords:tomato;abscisic acid;SlAREB1transcription factor;ChIP-Seq;fruit ripening
研究领域:
植物生物学
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分子遗传学
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转录组学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2018
·Vol. 9
·期 10
·1-16
·
IF 5.638
Niu Xiuran,Su Linjia,Qi Shanshan,Gao Zhihui,Zhang Qing,Zhang Sihe
Chaperone-assisted proteasome degradation of oncogenic protein acts as an upstream signal controlling tumorigenesis and progression. The understanding of the co-regulation of chaperone and oncoprotein of endocytosis pathways is extremely limited. In this study, we showed for the first time that proto-Dbl ( dbl proto-oncogene product) is co-enriched with mitochondrial chaperone GRP75 in endocytosis vesicles from ovarian cancer cells. onco-Dbl, produced by oncogenic mutation/degradation of proto-Dbl, markedly enhanced cellular macropinocytosis but suppressed clathrin-mediated endocytosis and clathrin-independent endocytosis pathways, presenting a derailed endocytosis phenotype. GRP75 was associated with proto-Dbl inside cells and modulated Dbl-driven endocytosis derailed by a co-regulatory mode. In spite of not being a component of the Hsc70/Hsp90/proto-Dbl complex, the degradation of proto-Dbl was promoted by GRP75 through the CHIP-mediated ubiquitin–proteasome pathway, of which GRP75 acts as a cooperator with CHIP but also acts as a competitor to Hsc70 and Hsp90 in the multiple chaperones-assisted pro-folding/pro-degradation machinery. Knockdown or inhibition of GRP75 attenuated proto-Dbl degradation and reduced the onco-Dbl level, which differentially impaired Rho GTPases activation and therefore shifted the endocytosis-derailed phenotype. Our data uncovered a novel GRP75-Dbl endocytosis regulatory axis and provided an alternative using chaperone inhibitor to shut down the oncoprotein-driven endocytosis derailment mechanism.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Weijia Zhou,Chengjun Zhu,Peiliang Shen,Jacqueline F. Wang,Gaoshuang Zhu,Yuanyuan Jia,Yueyao Wu,Siliang Wang,Jia Sun,Fang Yang,Yanni Song,Xin Han,Xiaoxiang Guan
Circulating tumor cell clusters/micro-emboli (CTM) possess greater metastatic capacity and survival advantage compared to individual circulating tumor cell (CTC). However, the formation of CTM subtypes and their role in tumor metastasis remain unclear. In this study, we used a microfluidic Cluster-Chip with easy operation and high efficiency to isolate CTM from peripheral blood, which confirmed their correlation with clinicopathological features and identified the critical role of CTC-platelet clusters in breast cancer metastasis. The correlation between platelets and CTM function was further confirmed in a mouse model and RNA sequencing of CTM identified high-expressed genes related to hypoxia stimulation and platelet activation which possibly suggested the correlation of hypoxia and CTC-platelet cluster formation. In conclusion, we successfully developed the Cluster-Chip platform to realize the clinical capture of CTMs and analyze the biological properties of CTC-platelet clusters, which could benefit the design of potential treatment regimens to prevent CTM-mediated metastasis and tumor malignant progression.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Siyu Xu,Yu Lei,Mulin Wei,Zhixiang Fang,Yue Cheng,Gang Zhao,Zhongrong Chen
Oocyte cryopreservation plays a crucial role in safeguarding female fertility in clinical practice. However, commonly used cryopreservation methods involving tedious and time-consuming procedures, as well as uncontrolled variability between operators, which can easily lead to cell damage. Here, a novel method for cryopreserving oocytes using a transparent alumina ceramics-based microfluidic chip is developed, which provides an integrated platform for cryoprotectants (CPAs) loading/unloading, as well as freeze-thaw process and storage. The cryopreservation protocol is optimized to significantly simplify the overall process, reduce CPA osmotic damage, and achieve high-performance oocyte cryopreservation. The survival rate of oocyte cryopreserved with this method reached 86.23%. In comparison to conventional method, the recovered oocytes exhibit structural stability, functional integrity, genetic normality and higher developmental capacity. The study offers a low-cost, easy-to-operate, high-performance, on-chip semi-automatic cryopreservation technique for oocytes, which is of great significance for standardizing and automating the cryopreservation of female fertility, and has important potential for translational applications.
研究领域:
生殖医学
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生物工程
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材料科学
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产品关联
DOI
高影响因子
NUCLEIC ACIDS RESEARCH
·
2020
·Vol. 48
·期 19
·10768-10784
·
IF 11.502
Sun Ge,Wang Chunyu,Wang Shengli,Sun Hongmiao,Zeng Kai,Zou Renlong,Lin Lin,Liu Wei,Sun Ning,Song Huijuan,Liu Wensu,Zhou Tingting,Jin Feng,Shan Zhongyan,Zhao Yue
Estrogen receptor alpha (ERα) signaling pathway is essential for ERα-positive breast cancer progression and endocrine therapy resistance. Bromodomain PHD Finger Transcription Factor (BPTF) associated protein of 18kDa (BAP18) has been recognized as a crucial H3K4me3 reader. However, the whole genomic occupation of BAP18 and its biological function in breast cancer is still elusive. Here, we found that higher expression of BAP18 in ERα-positive breast cancer is positively correlated with poor prognosis. ChIP-seq analysis further demonstrated that the half estrogen response elements (EREs) and the CCCTC binding factor (CTCF) binding sites are the significant enrichment sites found in estrogen-induced BAP18 binding sites. Also, we provide the evidence to demonstrate that BAP18 as a novel co-activator of ERα is required for the recruitment of COMPASS-like core subunits to the cis-regulatory element of ERα target genes in breast cancer cells. BAP18 is recruited to the promoter regions of estrogen-induced genes, accompanied with the enrichment of the lysine 4-trimethylated histone H3 tail (H3K4me3) in the presence of E2. Furthermore, BAP18 promotes cell growth and associates the sensitivity of antiestrogen in ERα-positive breast cancer. Our data suggest that BAP18 facilitates the association between ERα and COMPASS-like core subunits, which might be an essential epigenetic therapeutic target for breast cancer.
研究领域:
肿瘤学
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分子生物学
·
表观遗传学
·
癌症治疗
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2022
·
IF 9.231
Minglu Wang,Ying Wang,Xiangyang Li,Hongyan Zhang
The continuous intake of diethylstilbestrol (DES) residue seriously threatens the health of consumers, so the rapid and sensitive detection of DES is helpful for timely food safety warning. In this study, a photothermal-sensing microfluidic paper-based analytical chip (PT-Chip) was developed for effectively screening of DES residue in foods. Competitive inhibition immunochromatography was introduced and the composite of black phosphorus nanosheets and gold nanoparticles (BP-Au) was used as signal indicators. Then, the test area was irradiated by an 808 nm laser and the photothermal transduction signal was recorded by a thermal imager to achieve sensitive photothermal detection. The amount of DES was obtained by analyzing the temperature change curve of test area. The PT-Chip can achieve accurate quantification of DES with a detection limit of 0.1 μg/L. And the successful determination of DES in different food samples indicating that the PT-Chip can be used as a promising detection device.
研究领域:
分析化学
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纳米技术
·
食品科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2024
·
IF 4.4
Jingwen Shi,Wenda Jing,Yueyun He,Ying Huang
Despite decades of research, endometriosis remains a mysterious gynecological disease with unknown etiology and pathogenesis. Krüppel-like Factor 6 (KLF6), a transcription factor, has a wide expression profile and regulates a variety of biological processes. Here, we investigated the expression and function of KLF6 and its possible regulatory mechanisms in endometriosis. To determine the function of KLF6, knockdown and overexpression experiments were performed in eutopic endometrial stromal cells (EU-ESCs) and ectopic endometrial stromal cells (EC-ESCs), respectively. Cell viability, apoptosis, migration, invasion, and angiogenesis assays were conducted in ESCs. ChIP-sequencing and mRNA-sequencing were performed to investigate the functional mechanism of KLF6 in regulating ESCs. We found that KLF6 was highly expressed in eutopic endometrium of endometriosis patients, compared with ectopic endometrium. Similarly, the same was true in EU-ESCs, which was compared with EC-ESCs. Overexpression of KLF6 significantly suppressed EC-ESC proliferation, migration and invasion and induced cell apoptosis, while knockdown of KLF6 resulted in the opposite effects on EU-ESCs. Overexpression of KLF6 significantly inhibited EC-ESC angiogenesis. Mechanistically, the results of ChIP sequencing and mRNA sequencing revealed that CTNNB1 may be a transcriptional target regulated by KLF6. Reintroduction of KLF6 reversed the effects of KLF6 knockdown on EU-ESCs. KLF6 inhibited the proliferation, migration and angiogenesis of EC-ESCs by inhibiting the expression of CTNNB1. Our findings provided a new perspective on the role of KLF6 in endometriosis progression and inspire potential targeted therapeutic strategies.
研究领域:
妇科学
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分子生物学
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转录因子
·
疾病发病机制
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENT
·
2024
·
IF 3.7
Yu Meng,Thorner Konrad,Parameswaran Sreeja,Wei Wei,Yu Chuyue,Lin Xinhua,Kopan Raphael,Hass Matthew R.
The conserved Runt-related (RUNX) transcription factor family are master regulators of developmental and regenerative processes. Runx1 and Runx2 are expressed in satellite cells (SC) and in skeletal myotubes. Conditional deletion of Runx1 in adult SC negatively impacted self-renewal and impaired skeletal muscle maintenance even though Runx2 expression persisted. Runx1 deletion in C2C12 cells that retain Runx2 expression identified unique molecular functions of Runx1 that cannot be compensated by Runx2. The reduced myoblast fusion in vitro caused by Runx1 loss was due in part to ectopic expression of Mef2c, a target repressed by Runx1 . Structure-function analysis demonstrated that the Ets-interacting MID/EID region of Runx1, absent from Runx2, is critical to Runx1 myoblast function and for Etv4 binding. Analysis of ChIP-seq datasets from Runx1 (T-cells, muscle) versus Runx2 (preosteoblasts) dependent tissues identified a composite Ets:Runx motif enriched in Runx1 -dependent tissues. The Ets:Runx composite motif was enriched in peaks open exclusively in ATAC-seq datasets from WT cells compared to ATAC peaks unique to Runx1KO cells. Thus, engagement of a set of targets by the RUNX1/ETS complex define the non-redundant functions of Runx1 .
研究领域:
分子生物学
·
细胞生物学
·
转录因子
·
肌肉再生
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Ke Yang,Jingyu Pan,Guoqing Deng,Changyi Hua,Cancan Zhu,Yong Liu,Ling Zhu
Mobile sensing enabled by MS 2 technology, which integrates microfluidic and smartphone components, has seen many applications in recent years. In this direction, we developed an MS 2 platform (an integrated kit) for nucleic acid assay, which included a chitosan-modified minimalistic microfluidic chip (CM 3 -chip), a smartphone-based fluorescence detector (SF-detector), an APP for imaging and analysis, reagents, and accessories. Once the lysed sample was loaded into the CM 3 -chip modified by 1% concentration and 200–260 kDa molecular weight of chitosan, the following assay can be completed in approximately 1 h. The Mkit can detect 3 × 10° copies μL −1 of plasmid DNA and its polymerase chain reaction (PCR) efficiency was 96.8%. The CM 3 -chip equipped for the Mkit can enrich nucleic acid from the pH = 5 of lysis buffer, instead of using conventional adsorption mediums such as the magnetic beads and silica gel membranes, which could result in unexpected impurity residuals and tedious cleaning operations. In addition, the performance of the Mkit equipped with the pristine chip was demonstrated to perform poorer than that coupled with the CM 3 -chip in which the enriched nucleic acid can be all used for “ in-situ PCR”. The universality, selectivity, and user-friendliness of the Mkit were also validated. We finally demonstrated the feasibility of the Mkit for testing artificially prepared infected samples. H5N6 and IAV-infected saliva samples provided the limits of detection of 5 × 10 2 copies mL −1 and 3.24 × 10 2 copies mL −1 per chamber, respectively. The streamlined assay and compact device should enable the great potential of the Mkit in research and potential diagnostic uses.
研究领域:
生物技术
·
微流控
·
分子生物学
·
即时诊断
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Yujie Zhang,Yuan Zhao,Zhenchong Sun,Chuanfeng An,Guoshuang Zheng,Yi Shen,Xingyu Zhu,Changle Ren,Lijun Zhang,Tao Chen,Yonggang Zhang,Jeroen JJP. van den Beucken,Jianru Xiao,Yang Zhang,Huanan Wang
Bone remodeling is governed by the basic multicellular unit (BMU) and plays a crucial role in both normal bone function and pathological conditions (e.g. osteoporosis). Unfortunately, our understanding of the bone remodeling process is limited as current models do not allow dynamic events in the BMU to be systematically and spatiotemporally analyzed. Leveraging microfluidic and stem cell technologies, we developed an bone-on-a-chip model that enables the dynamic co-culture of osteoblasts (OBs) and osteoclasts (OCs) in a spatiotemporal context. This model faithfully recapitulates critical aspects of the bone remodeling process, including cell migration and differentiation into OBs and OCs, as well as their delicate coupling within the BMU during bone regeneration, homeostasis, and in osteoporotic conditions. RNA sequencing analyses revealed that our bone remodeling-on-a-chip model exhibits more pronounced osteoporotic features compared to conventional OB-OC co-cultures, closely resembling the pathological bone remodeling observed in osteoporotic mice. Notably, our bone remodeling-on-a-chip model accurately predicts the clinically observed antiresorptive effects of two anti-osteoporosis drugs. Therefore, our bone remodeling-on-a-chip model stands poised as an advanced platform to enhance our understanding of bone pathophysiology and offers a promising alternative to current drug testing in bone-related diseases. Statement of Significance Bone remodeling, governed by the basic multicellular unit (BMU), is crucial for bone development. Current models fail to analyze dynamic events within the BMU systematically and spatiotemporally. We developed a microfluidic bone remodeling-on-a-chip model for the co-culture of osteoblasts (OBs) and osteoclasts (OCs). This model replicates key aspects of bone remodeling, including the migration, differentiation, and coupling of OBs and OCs under various conditions. It closely mirrors pathological bone remodeling in osteoporotic mice and demonstrates reliable drug testing for anti-osteoporosis drugs. This advanced platform enhances our understanding of bone pathophysiology and offers a promising drug testing model for bone-related diseases.
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产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2020
·Vol. 36
·期 4
·694-698
·
IF 1.063
Li La,Chen Di,Shen Guozhen
Flexible on-chip microsupercapacitors(MSCs) are highly desired for integrated wearable or portable electronics due to their advantages of small size, high power density, easy integration, long lifespan, high security, and flexibility. The output voltage of MSCs can be improved by designing MSC arrays, which could further expand their application fields. In this work, we proposed a facile laser direct cutting method to prepare an on-chip flexible MSC array using Ti 3 C 2 T x MXene as both current collector and electrode materials. The designed MSC in PVA/H 2 SO 4 all-solid-state gel electrolyte exhibits a large volume/areal capacitance of 770.72 F/cm 3 (46.24 mF/cm 2 ) at a scan rate of 20 mV/s, a high energy density of 68.51 mW·h/cm 3 at a power density of 6.16 W/cm 3 , excellent cycling stability with capacitance retention of 98.50% after 10000 charge/discharge cycles. The MSC also shows superior flexibility and stability even after repetition of charge/discharge cycles under the convex and concave bending states. In addition, the assembled MSC array(4 in series) provides a high voltage of 3.2 V, which could easily power a purple light-emitting diode more than 10 min, demonstrating its potential application in integrated portable/wearable devices.
研究领域:
材料科学
·
能源存储
·
纳米技术
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）