Email: xshen“at”tsinghua.edu.cn

Lab Tel：+86-10-62798513

http://www.med.tsinghua.edu.cn/Person?method=102&perId=24

RESEARCH INTERESTS

  Our main research interest is to understand how the noncoding portions of the genome, particularly noncoding RNAs (ncRNAs) and genomic repeats, act with their associated proteins to shape distinct epigenetic and cellular states during stem-cell differentiation and in development. In the past years, we have rigorously investigated novel aspects of ncRNAs, genomic repeats, and RNA-binding proteins in transcription and chromatin regulation in mouse embryonic stem cells (ESCs) and embryos, and revealed important paradigms of noncoding RNA-mediated regulation in transcription and chromatin structure.

  We will continue to elucidate the regulation and function of noncoding RNA, RBPs and genomic repeats at the molecular and systems levels by using high-throughput integrative approaches across proteomic and genomic systems, together with state-of-art genome editing, imaging, biochemical and single-cell techniques. Our work will help to elucidate fundamental aspects of chromatin and developmental biology, and provide an important framework in which to consider transcription control and cell-fate determination in normal development and disease, and perhaps suggest innovative approaches for disease intervention and to assist manipulation of cell fates for regenerative medicine in future studies.

1. Noncoding RNA and RNA-binding proteins in transcription and chromatin regulation

2. Genomic repeats in genome organization and structure

3. Regulatory networks in stem-cell pluripotency and embryonic development

SELECTIVE PUBLICATIONS

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. 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. (* co-corresponding)

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.