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En-Kui DUAN, Ph. D.

embryo implantation,epidermal development and skin stem cell regulation


Co-workers: Yujing Cao, Ying Zhang, Xiaohua Lei, Huishan Zhang, Zhonghong Cao, Xudong Zhang, Na Li, Yufang Zhang, Junchao Shi, Yongcun Qu, Jingjing Qian, Qian Zhao

• DUAN Group website

 

  1. he distribution of intrauterine embryo implantation site(s) in most mammalian species shows remarkably constant patterns: in monotocous species such as humans, an embryo tends to implant in the uterine fundus; in polytocous species such as rodents, embryos implant evenly along the uterine horns. These long-time evolved patterns bear great biological significance because disruption of these patterns can have adverse effects on pregnancies. Before the initiation of embryo implantation, the embryos were transported under the uterine peristaltic movements and carried by the uterine fluids. We’re interested in the molecular/biomechanical regulations of uterine contraction and intrauterine fluids regulation that are critical for “on site” embryo implantation. Also, we’re investigating the environmental/hormonal/pharmacological factors that will disrupt normal intrauterine embryo distribution and adversely affect pregnancy outcome.

  2. The success of embryo implantation is a critical step towards further embryo development and pregnancy outcome. Previous studies have indicated that the cause of many mid-term miscarriage/abnormal pregnancy was seeded very early at the onset of embryo implantation. Normal embryo implantation involves the embryo’s development into an implantation-competent blastocyst and the synchronized transformation of uteri into a receptive stage, which is referred to as “implantation window”. An accurate hormonal environment and local “cross-talk” between the blastocyst and endometrium are required for the success of implantation. Particularly, a small estrogen surge before implantation is necessary to prepare the progesterone-primed uterus into receptive stage; we’re now investigating the downstream transcription factors that regulated by this estrogenic effects.

  3. Various types of stem cells exist in the skin and support skin regeneration, wound repair and homeostasis. Skin stem cells are also closely related to skin diseases and tumors. Besides their physiological and pathological functions, skin stem cells also make ideal models to study cellular signal transduction. Our group focuses on epidermal stem cells, dermal stem cells and hair follicle stem cells. We study the self-renewal and differentiation of these stem cells and investigate their “cross-talk” with the niches. We also try to explain their roles in skin physiology, hair follicle cycles and skin aging.



Schematic diagrams showing the process and regulatory factors of embryo distribution along the uterine longitudinal axis (mice).



Transient {beta}2-adrenoceptor activation confers pregnancy loss by disrupting embryo spacing at implantation



Diagram showing main steps of mammalian skin development and the focuses of our research

 

Plain english:
  Pregnancy loss is a common and painful condition for gestational women, accounting for 25-40% of total pregnancy, having become a serious social-medical issue worldwide. Both animal studies and clinical investigations have indicated that the cause of many mid-term miscarriage/abnormal pregnancy was seeded very early at the onset of embryo implantation. Normal embryo implantation requires accurate timing and locations within the uteri, abnormal intrauterine embryo distribution and timing are important cause for adverse embryo development and miscarriage. Our group use transgenic/knockout mice as model system, combining cellular, molecular and computational/biomechanical approaches to study the mechanisms how the embryos are transported to the optimal sites and how to initiate implantation process.
  Skin is the outer barrier for humans and all other animals that helps maintain the body temperature and protects the animal from dehydration and exterior damages. Mammalian skin consists of epidermis, dermis and subcutaneous tissues, and is abundant in appendages such as hair follicles and sweat glands. Various types of stem cells exist in the skin and support its physiological functions. Our group, on one hand, try to describe and explain the development of mammalian skin, using transgenic animal models and developmental-biology-specific methods. On the other hand, we also study skin stem cells, in order to elucidate their role in skin metabolism, wound healing and skin aging, as well as to explore their potential value in regenerative medicine.

 

Selected publications:

  1. Chen Q*, Yan W*, Duan E*. Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat Rev Genet. 2016 Dec;17(12):733-743.
  2. hen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, Feng G, Peng H, Zhang X, Zhang Y, Qian J, Duan E*, Zhai Q*, Zhou Q*. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. 2016 Jan 22;351(6271):397-400. (Highlight paper)
  3. Shi J, Chen Q, Li X, Zheng X, Zhang Y, Qiao J, Tang F, Tao Y*, Zhou Q*, and Duan E*. Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq. Development. 2015 142, 3468-3477. (Highlight paper)
  4. Zhao Q, Liu S, Zhang H, Li N, Wang X, Cao Y, Ning L, Duan E*, and Xia G*. Spatiotemporal Expression of p63 in Mouse Epidermal Commitment. Int J Mol Sci. 2015 Dec 10;16(12):29542-53.
  5. Zhang H, Zhang S, Zhao H, Qiao J, Liu S, Deng Z, Lei X, Ning L, Cao Y, Zhao Y, and Duan E*. Ovine Hair Follicle Stem Cells Derived from Single Vibrissae Reconstitute Haired Skin. Int J Mol Sci.2015 16, 17779-17797.
  6. Zhang S, and Duan E*. Epigenetic regulations on skin wound healing: implications from current researches. Ann Transl Med. 2015 3, 227
  7. Ning L, Lei X, Cao Y, Zhang Y, Cao Z, Chen Q, andDuan E*. Effect of Short-Term Hypergravity Treatment on Mouse 2-Cell Embryo Development.Microgravity Sci. Technol. 2015 27:465–471.
  8. Liu S, Wang X, Zhao Q, Liu S, Zhang H, Shi J, Li N, Lei X, Zhao H, Deng Z, Cao Y, Ning L, Xia G, Duan E*. Senescence of human skin-derived precursors regulated by Akt-FOXO3-p27KIP1/p15 INK4b signaling. Cell Mol Life Sci. 2015 Aug;72(15):2949-60.
  9. Deng Z, Lei X, Zhang X, Zhang H, Liu S, Chen Q, Hu H, Wang X, Ning L, Cao Y, Zhao T, Zhou J, Chen T, Duan E*. mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration. J Mol Cell Biol. 2015 Feb;7(1):62-72.
  10. 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.
  11. 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 Jun 27. doi: 10.1038/cr.2014.82. [Epub ahead of print](Cover story) .
  12. 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 Feb 24;6(2):172-174 (Cover story) .
  13. Wang X, Liu S, Zhao Q, Li N, Zhang H, Zhang X, LeiX, Zhao H, Deng Z, Qiao J, Cao Y, Ning L,Liu S*, Duan E* Three-dimensional hydrogel scaffolds facilitate in vitro self-renewal of human skin-derived precursors,Acta Biomaterialia, 2014 10(7):3177-3187.
  14. 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 Oct;34(5):1024-42 (Invited review) .
  15. 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(11):1609-12. (Highlight paper) .
  16. Liu S, Liu S, Wang X, Zhou J, Cao Y, Wang F,Duan E*. The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro. Aging Cell. 2011 Aug;10(4):661-74.
  17. 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(6):4349-4356.
  18. 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 Jun;21(6):922-33.