- Ph.D., Institute of Zoology, Chinese Academy of Sciences, Beijing, China 2011
- M.D., Chongqing Medical University, Chongqing, China 2006
After I got my M.D. at Chongqing Medical University, I began my research with a project studying mouse embryo implantation at Institute of Zoology, Chinese Academy of Sciences, where I grown an interest in the molecular & biomechanical mechanisms to control intrauterine embryo localization and embryo orientation. After a twisted and exciting journey of discovery, I ended up to study water channels (aquaporins, AQPs) in reproductive system, with a serendipitous discovery of AQP3's role in sperm osmoadaptation, which turned out to be my Ph.D thesis. After the experience of working on sperm, I moved on to study the sperm-borne information (particularly those aside from DNA), and found a novel class of tRNA-derived small RNAs (tsRNAs), also known as tRFs (tRNA fragments) that are highly enriched in mature sperm. The function of sperm tsRNAs as paternal epigenetic information carrier and related regulation mechanisms are the focuses of my current research. I also developed a keen interest on the origin (molecular and cellular) of early mammalian embryo symmetry-breaking before blastocyst formation, for which we are now utilizing the power of single-cell technology and mathematical modeling to study with.
1. Sperm epigenetics: hidden information in RNAs
We are fascinating about the tantalizing facts that some acquired traits during paternal exposure can be inherited to the offspring, which apparently involves epigenetic mechanisms and lead to an resurrected idea of "Lamarckian inheritance". We recently discovered that a subset of sperm tRNA-derived small RNAs (tsRNAs), mainly from 5′ tRNA halves and ranging in size from 30 to 34 nucleotide, represent a type of paternal epigenetic information carrier that contribute to intergenerational inheritance of diet-induced metabolic disorder. We are currently working on how sperm tsRNAs, as well as their RNA modifications and responsible enzymes, affect the process of embryo development that lead to offspring phenotypic changes.
2. Symmetry-breaking in mammalian early embryo: when and how?
In mammalian preimplantation embryo development, when the first asymmetry emerges and how it develops to direct distinct cell fates are two longstanding questions. It remains debatable whether the first bifurcation of cell fate emerges randomly at morula stage, or has been predetermined at earlier stages before morphological distinction. Combining single-cell RNA-seq analysis and mathematical modelling, we recently showed that the very first symmetry-breaking process involves both chance separation and defined transcriptional circuits, a new framework for our future detailed investigations.
3. Old dog, new tricks? novel function of Aquaporins beyond simple permeability
Aquaporin(s), also known as water channel(s), are a family of integral trans-membrane proteins that form pores in the membrane of cells, their presence increases cell membrane permeability to water, or other small molecules such glycerol. However, emerging evidence for AQPs in cell volume regulation, including our discovery of AQP3's role in sperm osmoadaptation, can not be fully explained by considering AQPs as inert pores simply for water permeability, but implicating AQPs as mechanosensors, especially in tissues with very low water permeability such as bladder, urethra etc.
(*Co-first authors; #Corresponding authors)
- Chen Q*, Shi J*, Tao Y, Zernicka-Goetz M#. Tracing the origin of heterogeneity and symmetry breaking in the early mammalian embryo. Nature Communications (2018) 9:1819.
- Shi J#, Ko EA, Sanders KM, Chen Q#, Zhou T#. SPORTS1.0: a tool for annotating and profiling non-coding RNAs optimized for rRNA- and tRNA- derived small RNAs. Genomics, Proteomics & Bioinformatics (2018) Apr;16(2):144-151
- Zhang Y*, Zhang X*, Shi J*, Tuorto F*, Li X*, Liu Y, Liebers R, Zhang L, Qu Y, Qian J, Pahima M, Liu Y, Yan M, Cao Z, Lei X, Cao Y, Peng H, Liu S, Wang Y, Zheng H, Woolsey R, Quilici D, Zhai Q, Li L, Zhou T, Yan W, Lyko F, Zhang Y#, Zhou Q#, Duan E#, Chen Q#. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nature Cell Biology (2018) 20, 535-540.
- Zhang Y, Shi J, Chen Q#. tsRNAs: new players in mammalian retrotransposon control. Cell Research. (2017) doi:10.1038/cr.2017.109
- Shi J, Zhang X, Liu Y, Chen Q#. Epigenetic information in gametes: gaming from before fertilization. Physics of Life Reviews. (2017) Mar;20:146-149.
- Zhang X*, Cozen AE*, Liu Y, Chen Q# , Lowe TM#. Small RNA Modifications: Integral to Function and Disease. Trends in Molecular Medicine. (2016) Dec;22(12):1025-1034.
- Chen Q#, Yan W#, Duan E#. Epigenetic inheritance of acquired traits via sperm RNAs and sperm RNA modifications. Nature Reviews Genetics. 2016, doi: 10.1038/nrg.2016.106
- Shi J*, Zhang Y*, Chen Q#. Molecular carriers of acquired inheritance: absence of evidence is not evidence of absence. Environmental Epigenetics. 2016 2 (2): dvw014
- Chen Q*,# , Yan M*, Cao Z*, Li X*, Zhang Y*, Shi J*, Peng H, Zhang X, Zhang Y, Duan E#, Zhai Q#, Zhou Q#, Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science DOI: 10.1126/science.aad7977. Published online Dec. 31 2015
- Shi J*, Chen Q*, #, Li X*, Zheng X*, Zhang Y, Qiao J, Tang F, Tao Y#, Zhou Q#, Duan E#. Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq. Development. 2015, 15;142(20):3468-77.
-Highlighted in Development: Revisiting blastomere equality. Development 2015 142: e2002
- Zhang Y*, Chen Q*, Zhang H*, Wang Q*, Rong L, Jin Y, Wang H, Ma T, Qiao J, Duan E. Aquaporin-mediated excessive intrauterine ﬂuid is a major contributor in hyper-estrogen induced aberrant embryo implantation. Cell Res. 2015; Jan,25(1):139-42.
- Zhang S, Kong S, Wang B, Cheng X, Chen Y, Wu W, Wang Q, Shi J, Zhang Y, Wang S, Lu J, Lydon JP, DeMayo F, Pear WS, Han H, Lin H, Li L, Wang H, Wang YL, Li B, Chen Q#, Duan E#, Wang H#. Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms. Cell Res (2014), 24:925-942.
-Cover Story & Highlighted by: Rbpj links uterine transformation and embryo orientation. Cell Res. (2014); 24:1031-1032
- Zhang Y, Zhang Y, Shi J, Zhang H, Cao Z, Gao X, Ren W, Ning Y, Ning L, Cao Y, Chen Y, Ji W, Chen Z#, Chen Q#, Duan E#. Identification and characterization of an ancient class of small RNAs enriched in serum associating with active infection. J Mol Cell Biol (2014), 6:172-174.
-Cover Story & Editor's Recommendation: Characterization of serum-enriched tsRNAs.
- Chen Q*, Zhang Y*, Elad D, Jaffa AJ, Cao Y, Ye X#, Duan E#. Navigating the site for embryo implantation: Biomechanical and molecular regulation of intrauterine embryo distribution. Mol Aspects Med (2013) 34:1024-42.
- Peng H, Shi J, Zhang Y, Zhang H, Liao S, Li W, Lei L, Han C, Ning L, Cao Y, Zhou Q, Chen Q#, Duan E#. A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm. Cell Res (2012), 22: 1609-1612.
-Highlighted by: A load of small RNAs in the sperm - how many bits of hereditary information? Cell Res. (2013);23:18-19.
- Chen Q, Duan EK. Aquaporins in sperm osmoadaptation: an emerging role for volume regulation. Acta Pharmacol Sin (2011), 32: 721-4
- Chen Q*, Peng H*, Lei L*, Zhang Y, Kuang H, Cao Y, Shi QX, Ma T, Duan E#. Aquaporin3 is a sperm water channel essential for postcopulatory sperm osmoadaptation and migration. Cell Res (2011), 21: 922-933.
- Chen Q*, Zhang Y*, Peng H, Lei L, Kuang H, Zhang L, Ning L, Cao Y, Duan E#. Transient β2-Adrenoceptor activation confers pregnancy loss by disrupting embryo spacing at implantation. J Biol Chem (2011), 286: 4349-4356.
- Chen Q*, Zhang Y*, Lu J, Wang Q, Wang S, Cao Y, Wang H, Duan E. Embryo-uterine cross-talk during implantation: the role of Wnt signaling. Mol Hum Reprod (2009), 15: 215-221.
- Chen Q, Peng H, Zhang Y, Lei L, Cao Y, Duan E. Embryo implantation: a time for recalling and forwarding. Chinese Sci Bull (2009),54: 4083-93.
- Kuang H*, Chen Q* , Zhang Y, Zhang L, Peng H, Ning L, Cao Y, Duan E#.The cytokine gene, CXCL14, restricts human trophoblast cell invasion by suppressing gelatinase activity. Endocrinology (2009), 150: 5596-5605.
- Kuang H*, Chen Q* , Fan X, Zhang Y, Zhang L, Peng H, Cao Y, Duan E#. CXCL14 inhibits trophoblast outgrowth via a paracrine/ autocrine manner during early pregnancy in mice. J Cell Physiol (2009), 221: 448-457.