Browsing by Author "Yang, Hui"

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    ASXL1 interacts with the cohesin complex to maintain chromatid separation and gene expression for normal hematopoiesis
    (American Association for the Advancement of Science, 2017-01-20) Li, Zhaomin; Zhang, Peng; Yan, Aimin; Guo, Zhengyu; Ban, Yuguang; Li, Jin; Chen, Shi; Yang, Hui; He, Yongzheng; Li, Jianping; Guo, Ying; Zhang, Wen; Hajiramezanali, Ehsan; An, Huangda; Fajardo, Darlene; Harbour, J. William; Ruan, Yijun; Nimer, Stephen D.; Yu, Peng; Chen, Xi; Xu, Mingjiang; Yang, Feng-Chun; Department of Pediatrics, IU School of Medicine
    ASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice; however, the underlying molecular mechanisms remain unclear. We report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromatid segregation and regulate gene expression. Loss of Asxl1 impairs the cohesin function, as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. Chromatin immunoprecipitation followed by DNA sequencing data revealed that ASXL1, RAD21, and SMC1A share 93% of genomic binding sites at promoter regions in Lin-cKit+ (LK) cells. We have shown that loss of Asxl1 reduces the genome binding of RAD21 and SMC1A and alters the expression of ASXL1/cohesin target genes in LK cells. Our study underscores the ASXL1-cohesin interaction as a novel means to maintain normal sister chromatid separation and regulate gene expression in hematopoietic cells.
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    Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations
    (Cold Spring Harbor Laboratory Press, 2018-04) Shah, Maitri Y.; Ferracin, Manuela; Pileczki, Valentina; Chen, Baoqing; Redis, Roxana; Fabris, Linda; Zhang, Xinna; Ivan, Cristina; Shimizu, Masayoshi; Rodriguez-Aguayo, Cristian; Dragomir, Mihnea; Van Roosbroeck, Katrien; Almeida, Maria Ines; Ciccone, Maria; Nedelcu, Daniela; Cortez, Maria Angelica; Manshouri, Taghi; Calin, Steliana; Muftuoglu, Muharrem; Banerjee, Pinaki P.; Badiwi, Mustafa H.; Parker-Thornburg, Jan; Multani, Asha; Welsh, James William; Estecio, Marcos Roberto; Ling, Hui; Tomuleasa, Ciprian; Dima, Delia; Yang, Hui; Alvarez, Hector; You, M. James; Radovich, Milan; Shpall, Elizabeth; Fabbri, Muller; Rezvani, Katy; Girnita, Leonard; Berindan-Neagoe, Ioana; Maitra, Anirban; Verstovsek, Srdan; Foddle, Riccardo; Bueso-Ramos, Carlos; Gagea, Mihai; Manero, Guillermo Garcia; Calin, Goerge A.; BioHealth Informatics, School of Informatics and Computing
    The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
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    Engineering human ventricular heart muscles based on a highly efficient system for purification of human pluripotent stem cell-derived ventricular cardiomyocytes
    (BMC, 2017-09-29) Li, Bin; Yang, Hui; Wang, Xiaochen; Zhan, Yongkun; Sheng, Wei; Cai, Huanhuan; Xin, Haoyang; Liang, Qianqian; Zhou, Ping; Lu, Chao; Qian, Ruizhe; Chen, Sifeng; Yang, Pengyuan; Zhang, Jianyi; Shou, Weinian; Huang, Guoying; Liang, Ping; Sun, Ning; Pediatrics, School of Medicine
    Background Most infarctions occur in the left anterior descending coronary artery and cause myocardium damage of the left ventricle. Although current pluripotent stem cells (PSCs) and directed cardiac differentiation techniques are able to generate fetal-like human cardiomyocytes, isolation of pure ventricular cardiomyocytes has been challenging. For repairing ventricular damage, we aimed to establish a highly efficient purification system to obtain homogeneous ventricular cardiomyocytes and prepare engineered human ventricular heart muscles in a dish. Methods The purification system used TALEN-mediated genomic editing techniques to insert the neomycin or EGFP selection marker directly after the myosin light chain 2 (MYL2) locus in human pluripotent stem cells. Purified early ventricular cardiomyocytes were estimated by immunofluorescence, fluorescence-activated cell sorting, quantitative PCR, microelectrode array, and patch clamp. In subsequent experiments, the mixture of mature MYL2-positive ventricular cardiomyocytes and mesenchymal cells were cocultured with decellularized natural heart matrix. Histological and electrophysiology analyses of the formed tissues were performed 2 weeks later. Results Human ventricular cardiomyocytes were efficiently isolated based on the purification system using G418 or flow cytometry selection. When combined with the decellularized natural heart matrix as the scaffold, functional human ventricular heart muscles were prepared in a dish. Conclusions These engineered human ventricular muscles can be great tools for regenerative therapy of human ventricular damage as well as drug screening and ventricular-specific disease modeling in the future. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0651-x) contains supplementary material, which is available to authorized users.