Research Summary
The long-term research goal of the Wang laboratory is to understand the molecular mechanisms that regulate cardiovascular and hematopoietic differentiation of pluripotent stem cells (PSCs), including embryonic stem (ES) cells and induced-pluripotent stem (iPS) cells. Pluripotent stem cells hold great potential for regenerative medicine, and gene therapy. Defining the molecular links between differentiation outcomes will provide important information for designing rational methods of stem cell manipulation.
Lab
The Wang lab focuses on the signals that direct the differentiation of pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem (iPS) cells, into hematopoietic and cardiovascular cells. Pluripotent stem cells hold great potential for regenerative medicine. A significant effort in the lab is underway to generate hematopoietic cells, such as megakaryocytes and platelets, from human iPS cells. Recently, Wang's team established a system to characterize the common precursors of hematopoietic and endothelial cells (hemangioblast or hemogenic endothelial cells) in human pluripotent stem cells. By transplanting endothelial cells derived from human pluripotent cells into immunodeficient mice, his researcher team showed these cells form functional blood vessels. Therefore, it is possible that endothelial cells from patient specific iPS cells could provide a cellular source for vascular regeneration in ischemic tissue. The team also investigates the niche function of endothelial cells in regulating cardiomyocyte development from pluripotent stem cells.
Core Facility:
Ross Flow Cytometry
Selected Publications
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Wang Z, Zhang Y, Kamen D, Lees E, Ravid K. Cyclin D3 is essential for megakaryocytopoiesis. Blood. 1995, 86:3783-8.
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Zhang Y, Wang Z, Ravid K. The cell cycle in polyploid megakaryocytes is associated with reduced activity of cyclin B1-dependent cdc2 kinase. J Biol Chem. 1996, 27:4266-72.
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Wang Z, Sicinski P, Weinberg RA, Zhang Y, Ravid K. Characterization of the mouse cyclin D3 gene: exon/intron organization and promoter activity. Genomics. 1996, 35:156-63.
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Zhang Y, Wang Z, Liu DX, Pagano M, Ravid K. Ubiquitin-dependent degradation of cyclin B is accelerated in polyploid megakaryocytes. J Biol Chem. 1998, 273:1387-92.
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Wang Z, Zhang Y, Lu J, Sun S, and Ravid K. Mpl ligand enhances the transcription of the cyclin D3 gene: a potential role for Sp1 transcription factor. Blood. 1999, 93:4208-21.
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Zhang Y, Sun S, Wang Z, Thompson A, Kaluzhny Y, Zimmet J, Ravid K. Signaling by the Mpl receptor involves IKK and NF-kappaB. J Cell Biochem. 2002, 85:523-35.
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Poznansky MC, Olszak IT, Evans RH, Wang Z, Foxall RB, Olson DP, Weibrecht K, Luster AD, Scadden DT. Thymocyte emigration is mediated by active movement away from stroma- derived factors. J Clin Invest. 2002, 109:1101-10.
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Wang Z, Miura N, Bonelli A, Mole P, Carlesso N, Olson DP, Scadden DT. Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. Blood. 2002, 99:2740-7.
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Wang Z, Shao Y., Cohen K., Mole P., Dombkowski D. and Scadden DT. Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels. Blood. 2004, 103:100-9.
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Li ZJ, Wang Z, Zheng YZ, Xu B, Yang RC, Scadden DT and Han HC. Kinetic Expression of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) during Embryonic Stem Cell differentiation. J Cell Biochem. 2005, 95:559-70.
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Chen T, Bai H, Shao Y, Arzigian M, Janzen V, Attar E, Xie Y, Scadden DT and Wang ZZ. Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro. Stem Cells. 2007; 25:392-401.
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Wang ZZ#, Au P, Chen T, Shao Y, Daheron LM, Bai H, Arzigian M, Fukumura D, Jain RK#and Scadden DT#. Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nat Biotechnol. 2007; 25:317-8. (#co-corresponding authors)
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Shao L, Feng W, Sun Y, Bai H, Liu J, Currie C, Kim J, Gama R, Wang Z, Qian Z, Liaw L, and Wu WS. Generation of iPS cells using defined factors linked via the self-cleaving 2A sequences in a single open reading frame. Cell Res. 2009; 19:296-306.
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Bai H, Gao Y, Arzigian M, Wojchowski DM, Wu WS, Wang ZZ. BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway. J Cell Biochem. 2010; 109(2):363-74.
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Sun Y, Shao L, Bai H, Wang ZZ, and Wu WS. Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration. Blood. 2010; 115(9):1709-17.
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Kuang SQ, Bai H, Fang ZH, Lopez G, Yang H, Tong WG, Wang ZZ, and Garcia-Manero G. Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia. Blood. 2010; 115(12):2412-9.
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Shao L, Sun Y, Zhang Z, Feng W, Gao Y, Cai Z, Wang ZZ, Look AT, and Wu WS. Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation. Blood. 2010; 115(23):4707-14.
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Jiang H, Lin X, Feng Y, Xie Y, Han J, Zhang Y, Wang ZZ, Chen T. Hemato-endothelial differentiation from lentiviral-transduced human embryonic stem cells retains durable reporter gene expression under the control of ubiquitin promoter. Cytotechnology. 2010; 62(1):31-42.
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Chen K, Bai H, Arzigian M, Gao YX, Bao J, Wu WS, Wu L, Wang ZZ. Endothelial cells regulate cardiomyocyte development from embryonic stem cells. J Cell Biochem. 2010; 111(1):29-39.
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Zhang Z, Gao YX, Gordon A, Wang ZZ, Qian Z, Wu WS. Efficient generation of fully reprogrammed human iPS cells via polycistronic retroviral vector and a new cocktail of chemical compounds. PLoS One. 2011; 6(10):e26592.
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Bai H, Chen K, Gao YX, Arzigian M, Xie YL, Malcosky C, Yang YG, Wu WS, Wang ZZ. Bcl-xL enhances single-cell survival and expansion of human embryonic stem cells without affecting self-renewal. Stem Cell Res. 2012; 8(1):26-37.
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Tang Y, Bai H, Urs S, Wang Z, Liaw L. Notch1 activation in embryonic VE-cadherin populations selectively blocks hematopoietic stem cell generation and fetal liver hematopoiesis. Transgenic Res. 2013; 22(2):403-10.
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Dowell, KG, Simons AK, Wang ZZ, Yun K, Hibbs MA. Cell-Type-Specific Predictive Network Yields Novel Insights into Mouse Embryonic Stem Cell Self-Renewal and Cell Fate. PLoS One. 2013;8(2):e56810.
