首页 > 科学研究 > 造血干细胞发育和重编程研究课题组

> 课题组简介

  本课题组的主要研究方向是结合生物化学、基因组学方法和动物模型,研究正常及疾病相关造血干细胞(HSC)自我更新和分化过程中基因表达调控的分子机制,并基于体细胞重编程原理,发展体外诱导和扩增病人特异的HSC的技术,用于治疗白血病以及其他血液疾病。本课题组在国际上首次克隆鉴定了组蛋白H3K36甲基转移酶SETD2,并揭示其在胚胎发育和胚胎干细胞分化过程中的作用;从白血病细胞中纯化鉴定了转录因子复合物AETFC并解析其调控基因表达和白血病干细胞自我更新的机制;建立了斑马鱼造血相关基因和表观遗传调控基因的发育表达谱。

> 课题组长:孙晓建、黄秋花


> 代表性论文

1. Man, N.; Sun, X. J.; Tan, Y.; Garcia-Cao, M.; Liu, F.; Cheng, G.; Hatlen, M.; Xu, H.; Shah, R.; Chastain, N.; Liu, N.; Huang, G.; Zhou, Y.; Sheng, M.; Song, J.; Yang, F. C.; Benezra, R.; Nimer, S. D.; Wang, L. Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin. Blood 2016, Epub.

2. Xie, Y.; Zhang, Y.; Jiang, L.; Zhang, M.; Chen, Z.; Liu, D.; Huang, Q. Disabled homolog 2 is required for migration and invasion of prostate cancer cells. Front Med 2015, 9, 312-321.

3. Sun, X. J.; Man, N.; Tan, Y.; Nimer, S. D.; Wang, L. The Role of Histone Acetyltransferases in Normal and Malignant Hematopoiesis. Front Oncol 2015, 5, 108.

4. Zhang, Y.; Xie, S.; Zhou, Y.; Xie, Y.; Liu, P.; Sun, M.; Xiao, H.; Jin, Y.; Sun, X.; Chen, Z.; Huang, Q.; Chen, S. H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm. Cell Rep 2014, 8, 1989-2002.

5. Du, T. T.; Xu, P. F.; Dong, Z. W.; Fan, H. B.; Jin, Y.; Dong, M.; Chen, Y.; Pan, W. J.; Ren, R. B.; Liu, T. X.; Deng, M.; Huang, Q. H. Setdb2 controls convergence and extension movements during zebrafish gastrulation by transcriptional regulation of dvr1. Dev Biol 2014, 392, 233-244.

6. Sun, X. J.; Wang, Z.; Wang, L.; Jiang, Y.; Kost, N.; Soong, T. D.; Chen, W. Y.; Tang, Z.; Nakadai, T.; Elemento, O.; Fischle, W.; Melnick, A.; Patel, D. J.; Nimer, S. D.; Roeder, R. G. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis. Nature 2013, 500, 93-97.

7. Hu, M.; Sun, X. J.; Zhang, Y. L.; Kuang, Y.; Hu, C. Q.; Wu, W. L.; Shen, S. H.; Du, T. T.; Li, H.; He, F.; Xiao, H. S.; Wang, Z. G.; Liu, T. X.; Lu, H.; Huang, Q. H.; Chen, S. J.; Chen, Z. Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling. Proc Natl Acad Sci U S A 2010, 107, 2956-2961.

8. Zhang, Q. Y.; Mao, J. H.; Liu, P.; Huang, Q. H.; Lu, J.; Xie, Y. Y.; Weng, L.; Zhang, Y.; Chen, Q.; Chen, S. J.; Chen, Z. A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia. Proc Natl Acad Sci U S A 2009, 106, 3378-3383.

9. Du, T. T.; Fu, Y. F.; Dong, M.; Wang, L.; Fan, H. B.; Chen, Y.; Jin, Y.; Chen, S. J.; Chen, Z.; Deng, M.; Huang, Q. H.; Liu, T. X. Experimental validation and complexity of miRNA-mRNA target interaction during zebrafish primitive erythropoiesis. Biochem Biophys Res Commun 2009, 381, 688-693.

10. Zhang, S. J.; Ma, L. Y.; Huang, Q. H.; Li, G.; Gu, B. W.; Gao, X. D.; Shi, J. Y.; Wang, Y. Y.; Gao, L.; Cai, X.; Ren, R. B.; Zhu, J.; Chen, Z.; Chen, S. J. Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia. Proc Natl Acad Sci U S A 2008, 105, 2076-2081.

11. Sun, X. J.; Xu, P. F.; Zhou, T.; Hu, M.; Fu, C. T.; Zhang, Y.; Jin, Y.; Chen, Y.; Chen, S. J.; Huang, Q. H.; Liu, T. X.; Chen, Z. Genome-wide survey and developmental expression mapping of zebrafish SET domain-containing genes. PLoS One 2008, 3, e1499.

12. Sun, X. J.; Wei, J.; Wu, X. Y.; Hu, M.; Wang, L.; Wang, H. H.; Zhang, Q. H.; Chen, S. J.; Huang, Q. H.; Chen, Z. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem 2005, 280, 35261-35271.

13. Song, H. D.; Sun, X. J.; Deng, M.; Zhang, G. W.; Zhou, Y.; Wu, X. Y.; Sheng, Y.; Chen, Y.; Ruan, Z.; Jiang, C. L.; Fan, H. Y.; Zon, L. I.; Kanki, J. P.; Liu, T. X.; Look, A. T.; Chen, Z. Hematopoietic gene expression profile in zebrafish kidney marrow. Proc Natl Acad Sci U S A 2004, 101, 16240-16245.