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沈晓骅

 

 

电子邮件:xshen(at)tsinghua(dot)edu(dot)cn

电话:+86-10-62798513

医学院个人主页链接:http://www.med.tsinghua.edu.cn/Person?method=102&perId=24

 

研究方向:非编码核酸和细胞命运调控

1. 基因组重复序列、非编码RNA、和RNA结合蛋白

2. 转录、染色质结构和功能

3. 多能性干细胞的调控网络

  我们长期感兴趣的问题是在发育过程中不同细胞状态是如何建立的?通过探索基因组中非编码核酸在染色质和基因表达调控中的新颖功能,从独特的视角来揭示干细胞功能和细胞命运决定的普适性规律。包括从系统和分子水平上探索非编码RNA、基因组重复序列和RNA结合蛋白,影响转录和表观遗传状态的新模式。其结果将为认识生命现象的本质、个体复杂性和人类疾病发生,提供创新性的理论基础。

  近年来主要成果包括:(1)非编码RNA顺式调控邻近转录是基因表达调控的一种普遍模式,为非编码RNA的功能预测提供概念性突破;(2)非编码RNA和RNA结合蛋白是染色质的重要成分,在转录过程中被招募并反馈调控转录和染色质结构;(3)基因组重复序列协同调控基因表达和染色质高级结构的新颖功能。

 

代表性论文

1.     Yin Y*, Lu JY, Zhang X, Shao W, Xu Y, Li P, Hong Y, Cui L, Shan G, Tian B, Zhang Q, Shen X*. U1 snRNP regulates chromatin retention of noncoding RNAs. (2020). Nature. 2020. 580(7801):147-150. (* co-corresponding)

2.     Lu JY, Shao W, Chang L, Yin Y, Li T, Zhang H, Hong Y, Percharde M, Guo L, Wu Z, Liu L, Liu W, Yan P, Ramalho-Santos M, Sun Y, Shen X. Genomic repeats categorize genes with distinct functions for orchestrated regulation. (2020). Cell Reports. 30(10):3296-3311.

3.     Zhang H, Wu Z, Lu JY, Huang B, Zhou H, Xie W, Wang J, Shen X. DEAD-box helicase 18 counteracts PRC2 to safeguard ribosomal DNA in pluripotency regulation. Cell Reports. 2020. 30(1):81-97.

4.         Liu L, Lu J.Y, Xing X, Li T, Li F, Yang X, Shen X. IDH1 fine-tunes cap-dependent translation initiation. J Mol Cell Biol. 2019. Oct 25; 11(10):816-828.

5.         Han X, Zhang J, Liu Y, Fan X, Ai S, Luo Y, Li X, Jin H, Luo S, Zheng H, Yue Y, Chang Z, Yang Z, Tang F, He A*, Shen X*. The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression HAND2. Development. 2019. 146, dev176198. (* co-corresponding)

6.         Bi X, Xu Y, Li T, Li X, Li W, Shao W, Wang K, Zhan G, Wu Z, Liu W, Yin Y, Lu J.Y., Wang L, Zhao J, Wu J, Na J, Li G, Li P, Shen X. RNA targets ribosome biogenesis factor WDR43 to chromatin for transcription and pluripotency control. Mol Cell. 2019. 75: 102-116.

7.         Liu L, Li T, Song G, He Q, Yin Y, Lu J.Y., Bi X, Wang K, Luo S, Chen YS, Yang Y, Sun BF, Yang YG, Wu J, Zhu H*, Shen X*. Insight into novel RNA-binding activities via large-scale analysis of lncRNA-bound proteome and IDH1-bound transcriptome. Nucleic Acids Res. 2019. 47(5): 2244-2262. (*co-corresponding)

8.         Percharde M, Lin CJ, Yin Y, Guan J, Peixoto GA, Bulut-Karslioglu A, Biechele S, Huang B, Shen X, Ramalho-Santos M. A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity. Cell. 2018. 174(2):391-405.

9.         Han X, Luo S, Peng G, Lu JY, Cui G, Liu L, Yan P, Yin Y, Liu W, Wang R, Chang Z, Na J, Jing N*, Shen X*. Mouse knockout models reveal largely dispensable but context-dependent functions of lncRNAs during development. 2018. J Mol Cell Biol. 10(2):175-178. (* co-corresponding)

10.     Yan P, Luo S, Lu JY, Shen X. Cis- and trans-acting lncRNAs in pluripotency and reprogramming. Current Opinion in Genetics & Development. 2017. 46:170-178.

11.     Luo S, Lu J, Liu L, Yin Y, Han X, Xu R, Wu B, Liu W, Yan P, Shao W, Chen C, Lu Z, Na J, Tang F, Wang J, Zhang Y.E. and Shen X. Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell. 2016. 18(5):637-52.

12.     Yin Y, Yan P, Lu J, Song G, Zhu Y, Li Z, Zhao Y, Shen B, Huang X, Zhu H, Orkin SH, Shen X. Opposing roles for the lncRNA Haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation. Cell Stem Cell. 2015. 16(5):504-16.

13.     Shen X, Kim W, Fujiwara Y, Simon MD, Liu Y, Mysliwiec MR, Yuan G, Lee Y, Orkin SH. Jumonji modulates Polycomb activity and self-renewal versus differentiation of stem cells. Cell. 2009. 139(7): 1303-1314.

14.     Shen X, Liu Y, Hsu Y, Fujiwara Y, Kim J, Mao X, Yuan G, and Orkin SH. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell. 2008. 32(4):491-502.

15.     Shen X, Ellis RE, Lee K, Liu C, Yang K, Solomon A, Yoshida H, Morimoto R, Kurnit DM, Mori K, and Kaufman RJ. Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. Cell. 2001. 107: 893-903.

 

 

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