Michael Q. Zhang

The University of Texas at Dallas

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Jin Gu

Tsinghua University

Mengyu Feng

Shanghai Maritime University

Lei You

Fujian Institute of Research on the Structure of Matter

Guangbing Xiong

Huazhong University of Science and Technology

Wenbo Guo

Tsinghua University

Wenfang Guan

Guilin University of Aerospace Technology

Yupei Zhao

Peking Union Medical College Hospital

Yueze Liu

Peking Union Medical College Hospital

Zhe Cao

Wuhan University

Gang Yang

Gansu Agricultural University

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Tsinghua University

Chinese Academy of Sciences

Peking University

Cold Spring Harbor Laboratory

Center for Life Sciences

University of Hong Kong

Harvard University

Howard Hughes Medical Institute

Chinese University of Hong Kong

Chinese Academy of Medical Sciences & Peking Union Medical College

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Antibiotics and antibiotics resistance genes in sewage treatment plants

T Zhang B Li Xuening Zhang Michael Q. Zhang

The 2010 International Symposium on Advanced Biological Engineering (ISABE 2010), Beijing, China, 23-25 July 2010.

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Author response: Super-resolution imaging of a 2.5 kb non-repetitive DNA in situ in the nuclear genome using molecular beacon probes

Yanxiang Ni Bo Cao Tszshan Ma Gang Niu Yingdong Huo

Molecular beacon

Nuclear DNA

10.7554/elife.21660.022

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Epigenetic modification of MiR-429 promotes liver tumour-initiating cell properties by targeting Rb binding protein 4

Gut (2014)

Liang Li Jing Tang Baohua Zhang Wen Yang Mi-yang Liu-Gao

Objective

Liver tumour-initiating cells (T-ICs) are critical for hepatocarcinogenesis. However, the underlying mechanism regulating the function of liver T-ICs remains unclear.

Methods

Tissue microarrays containing 242 hepatocellular carcinoma (HCC) samples were used for prognostic analysis. Magnetically activated cell sorting was used to isolate epithelial cell adhesion molecule (EPCAM)-positive cells. The gene expressions affected by miR-429 were determined by arrays. Co-immunoprecipitation was used to study interactions among retinoblastoma protein (RB1), Rb binding protein 4 (RBBP4) and E2F transcription factor 1 (E2F1). The DNA methylation status in CpG islands was detected by quantitative methylation analysis. miRNAs in microvesicles were isolated by a syringe filter system.

Results

The significant prognosis factor miR-429 was upregulated in HCC tissues and also in primary liver T-ICs isolated from clinical samples. The enrichment of miR-429 in EPCAM⁺ T-ICs contributed to hepatocyte self-renewal, malignant proliferation, chemoresistance and tumorigenicity. A novel functional axis involving miR-429, RBBP4, E2F1 and POU class 5 homeobox 1 (POU5F1 or OCT4) governing the regulation of liver EPCAM⁺ T-ICs was established in vitro and in vivo. The molecular mechanism regulating miR-429 expression, involving four abnormal hypomethylated sites upstream of the miR-200b/miR-200a/miR-429 cluster, was first defined in both EPCAM⁺ liver T-ICs and very early-stage HCC tissues. miR-429 secreted by high-expressing cells has the potential to become a proactive signalling molecule to mediate intercellular communication.

Conclusions

Epigenetic modification of miR-429 can manipulate liver T-ICs by targeting the RBBP4/E2F1/OCT4 axis. This miRNA might be targeted to inactivate T-ICs, thus providing a novel strategy for HCC prevention and treatment.

10.1136/gutjnl-2013-305715

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Figure S3 from Integrative Genomic Analysis of Gemcitabine Resistance in Pancreatic Cancer by Patient-derived Xenograft Models

Gang Yang Wenfang Guan Zhe Cao Wenbo Guo Guangbing Xiong

The analysis of correlation between drug responses and the highly mutated genes

10.1158/1078-0432.22479594

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Tables S1-S13 from Integrative Genomic Analysis of Gemcitabine Resistance in Pancreatic Cancer by Patient-derived Xenograft Models

Gang Yang Wenfang Guan Zhe Cao Wenbo Guo Guangbing Xiong

Tables S1-S13

10.1158/1078-0432.22479585

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Figure S5 from Integrative Genomic Analysis of Gemcitabine Resistance in Pancreatic Cancer by Patient-derived Xenograft Models

Gang Yang Wenfang Guan Zhe Cao Wenbo Guo Guangbing Xiong

Protein-protein interaction (PPI) network of DEmRNAs of PDXs before and after gemcitabine

10.1158/1078-0432.22479588

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Predicting full-length transcripts

Trends in biotechnology (2002)

Michael Q. Zhang

10.1016/s0167-7799(02)01977-7

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New Fusion Transcripts Identified in Normal Karyotype Acute Myeloid Leukemia

PLoS ONE (2012)

Hao Wen Yongjin Li Sami N. Malek Yeong C. Kim Jia Xu

Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analysis in 45 AML cases including 29 normal karyotype AML, 8 abnormal karyotype AML and 8 AML without karyotype informaiton. Our study identified 134 fusion transcripts, all of which were formed between the partner genes adjacent in the same chromosome and distributed at different frequencies in the AML cases. Seven fusions are exclusively present in normal karyotype AML, and the rest fusions are shared between the normal karyotype AML and abnormal karyotype AML. CIITA, a master regulator of MHC class II gene expression and truncated in B-cell lymphoma and Hodgkin disease, is found to fuse with DEXI in 48% of normal karyotype AML cases. The fusion transcripts formed between adjacent genes highlight the possibility that certain such fusions could be involved in oncological process in AML, and provide a new source to identify genetic markers for normal karyotype AML.

Fusion transcript

10.1371/journal.pone.0051203

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Optimizing STORM Imaging Conditions for Identifying Single MoleculesUnder Cellular Auto-fluorescence Background

Journal of Molecular Imaging (2016)

Bo Cao Tszshan Ma Gang Niu Danni Chen Jianjiang Hu

Stochastic Optical Reconstruction Microscopy (STORM) imaging of fluorophore-labeled single molecules in biological samples is interfered by unavoidable cellular auto-fluorescence. This situation is improved by pairing fluorophores with activator dyes, which enhances fluorescence signals but restricts its application in biomedical studies. To address this issue, we optimized STORM imaging conditions for sparsely-distributing Alexa-647 samples simultaneously illuminated by a 641-nm excitation and a 405-nm reactivation lasers. We found that, compared to a frame frequency of 46 Hz or 85 Hz in STORM imaging, low frequency (20 Hz) resulted in a relatively high background fluorescence but had no obvious effect on specific signals of Alexa-647 in cell-free samples. In fixed human cells, high frequency (85 Hz) was superior in distinguishing sparse Alexa-647 fluorophores from cellular autofluorescence. Furthermore, a small false discovery rate was achieved with the use of moderate but not intensive powers of excitation and reactivation lasers. With the selected rather than original frame frequency and laser intensity, low fluorescence background and high detection efficiency of fluorophores were obtained for cell samples sparsely labeled with a range of Alexa-647 concentrations. Therefore, this study optimized STORM imaging conditions and promoted detection sensitivity and efficiency of single molecules in cells in an activator dye-independent way.

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Fluorescence-lifetime imaging microscopy

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The transcriptome of human CD34⁺hematopoietic stem-progenitor cells

Proceedings of the National Academy of Sciences (2009)

Yeong C. Kim Qingfa Wu Jun Chen Zhenyu Xuan Yong-Chul Jung

Studying gene expression at different hematopoietic stages provides insights for understanding the genetic basis of hematopoiesis. We analyzed gene expression in human CD34(+) hematopoietic cells that represent the stem-progenitor population (CD34(+) cells). We collected >459,000 transcript signatures from CD34(+) cells, including the de novo-generated 3' ESTs and the existing sequences of full-length cDNAs, ESTs, and serial analysis of gene expression (SAGE) tags, and performed an extensive annotation on this large set of CD34(+) transcript sequences. We determined the genes expressed in CD34(+) cells, verified the known genes and identified the new genes of different functional categories involved in hematopoiesis, dissected the alternative gene expression including alternative transcription initiation, splicing, and adenylation, identified the antisense and noncoding transcripts, determined the CD34(+) cell-specific gene expression signature, and developed the CD34(+) cell-transcription map in the human genome. Our study provides a current view on gene expression in human CD34(+) cells and reveals that early hematopoiesis is an orchestrated process with the involvement of over half of the human genes distributed in various functions. The data generated from our study provide a comprehensive and uniform resource for studying hematopoiesis and stem cell biology.

10.1073/pnas.0903390106

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Citations (29)