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Da-Hua CHEN, Ph. D.

Regulation of primordial germ cell specification and stem cell fate determination


Co-workers: Weiqi Tan, Xiaona Wang, Wenqin Li, Ying Cheng, Hailong Wang, Guoqiang Zhang, Yuanxiang Zhu, Chaoyi Li, Zhenping Chen, Wenxin Zhang, Weini Li, Yuewan Luo, Yajie Gao, Gaobo Wei, Dongqiang Yuan, Jiawei Sun, Zhijie Cao, Lei Wang.

• GAO Group website

 

  The Chen lab (Group of Model Organism and Stem Cell Biology) was established in 2005, when the team leader Dr. Dahua Chen was recruited by Institute of Zoology, Chinese Academy of Sciences as a “one hundred-talent scholar”. In support of the grants from MOST, NSFC and CAS, the Chen lab has been focusing on studying the molecular mechanism underlying the regulation of germ cell development and germline stem cell fate determination using Drosophila and mouse as model systems. During the past several years, the Chen lab used Drosophila germline stem cells as a model system to investigate the mechanisms of how stem cell self-renewal and differentiation are regulated in vivo and published a series of papers in the leading journals such as Cell、Developmental Cell、Nature Communications、Journal of Cell Biology、PLoS Biology、Current Biology、PLoS Genetics、Development、Human Molecular Genetics、Stem Cell Reports, and made significant contributions to the field.



GSC Asymmetric Division controlled by gradient BMP response.



A simplified Hh signaling pathway network for mathematic modeling (Huang et al. PLoS Biology 2013)

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A proposed model of AGO3 Slicer function (Huang et al. Journal of Cell Biology 2014).



Dynamic of 6mA DNA modification in Drosophila genome (Zhang et al. Cell 2015).

 

 

Plain English:
  Germ cells are the only cells that are able to pass the genetic materials from one generation to the next. One of the most fundamental issues in developmental biology is how the germ cell development is regulated. The Drosophila and mouse germline system have provided heuristic models and brought many novel insights into the fields of germ cell developmental biology as well as stem cell biology.
  Currently, we are integrating genetic, molecular biology and biochemical approaches to pursue in-depth understanding of the regulatory mechanism(s) underlying germ cell development and germline stem cell fate determination.
  In the short-term, we are completing three ongoing projects: 1) understand molecular basis of protein modification in the regulation of germ cell development and germline stem cell fate; 2) elucidate molecular basis of translational control in germ cells; 3) to test the hypothesis of the potential crosstalk between protein modification regulation and translational control in germ cells.
  The long-term goal of my lab is to identify novel mechanisms involved in Drosophila germ cells and germline stem cells, which will certainly help us elucidate how germ cell development and stem cell fate are controlled by the elaborate regulation of gene circuitry.

 

Selected publications:

  1. Sun Q*, Huang S, Wang X, Zhu Y, Chen Z, Chen D*.(2015) N6 -methyladenine functions as a potential epigenetic mark in eukaryotes. Bioessays (Invited review)
  2. Zhang G, Huang H, Liu D, Cheng Y, Liu X, Zhang W, Yin R, Zhang D, Zhang P, Liu J, Li C, Liu B, Luo Y, Zhu Y, Zhang N, He S, He C, Wang H*, Chen D* (2015) N(6)-methyladenine DNA modification in Drosophila. Cell 161: 893-906
  3. Huang H, Li Y, Szulwach KE, Zhang G, Jin P*, Chen D* (2014) AGO3 Slicer activity regulates mitochondria-nuage localization of Armitage and piRNA amplification. The Journal of cell biology 206: 217-230
  4. Zhu G, Li Y, Zhu F, Wang T, Jin W, Mu W, Lin W, Tan W, Li W, Street RC, Peng S, Zhang J, Feng Y, Warren StephenT, Sun Q*, Jin P*, Chen D* (2014) Coordination of Engineered Factors with TET1/2 Promotes Early-Stage Epigenetic Modification during Somatic Cell Reprogramming. Stem Cell Reports 2: 253-261
  5. Huang S, Zhang Z, Zhang C, Lv X, Zheng X, Chen Z, Sun L, Wang H, Zhu Y, Zhang J, Yang S, Lu Y, Sun Q, Tao Y, Liu F, Zhao Y*, Chen D* (2013) Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover. PLoS biology 11: e1001721
  6. Xia L, Zheng X, Zheng W, Zhang G, Wang H, Tao Y*, Chen D* (2012) The niche-dependent feedback loop generates a BMP activity gradient to determine the germline stem cell fate. Curr Biol 22: 515-521
  7. Lu C, Lin L, Tan H, Wu H, Sherman SL, Gao F, Jin P*, Chen D* (2012) Fragile X premutation RNA is sufficient to cause primary ovarian insufficiency in mice. Human molecular genetics 21: 5039-5047
  8. Xia L, Jia S, Huang S, Wang H, Zhu Y, Mu Y, Kan L, Zheng W, Wu D, Li X, Sun Q, Meng A, Chen D* (2010) The Fused/Smurf complex controls the fate of Drosophila germline stem cells by generating a gradient BMP response. Cell 143: 978-990
  9. Yang Y, Xu S, Xia L, Wang J, Wen S, Jin P*, Chen D* (2009) The bantam microRNA is associated with drosophila fragile X mental retardation protein and regulates the fate of germline stem cells. PLoS genetics 5: e1000444
  10. Jiang X, Xia L, Chen D, Yang Y, Huang H, Yang L, Zhao Q, Shen L, Wang J, Chen D* (2008) Otefin, a nuclear membrane protein, determines the fate of germline stem cells in Drosophila via interaction with Smad complexes. Developmental cell 14: 494-506