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Qi ZHOU, Ph. D.

Mechanism of cell reprogramming, animal models and therapeutic cloning, stem cells and regenerative medicine.


Staff: Qi ZHOU, Liu WANG, Ying ZHANG, Jie HAO, Haifeng WAN, Jun WU, Rui FU, Yukai WANG
Postdoc: Guihai FENG, Wei ZHANG, Dawei YU, Jiaqiang WANG
Students:Baolong XIA, Xiaolong CUI, Libin WANG, Fei TENG, Xuepeng WANG, Weifang HAN, Yuanqing TAN, Peng CUI, Yufei LI, Yihuan MAO, Yuhuan LI, Zhengquan HE, Chenxin WANG, Chao LIU, Jilong REN, Ruoyu MA

• ZHOU Group website

 

  The research areas of our laboratory include: the mechanisms of cell reprogramming and cell fate control, obtaining and maintenance of stem cell pluripotency, etc. We are also dedicated to promoting the application of stem cells and regenerative medicine.

  We have derived and established embryonic stem (ES) cell lines from mouse, rat, monkey, and human, and have set up stable technical platforms for cell reprogramming technologies, including nuclear transfer and induced pluripotent stem (iPS) cell technology, for several species. We generated viable mice from iPS cells through tetraploid complementation, demonstrating that iPS cells have the similar pluripotency to that of ES cells. We also conducted a series of studies regarding transdifferentiation of cells of the same germ layer and of cells across germ layers, and tried, backed by the technical platforms we established, to explore the mechanisms underlying the somatic cell de-differentiation and transdifferentiation, to elucidate the events and key factors employed during cell fate conversion. We discovered and demonstrated a key gene-regulation region that may serve as a molecular marker for evaluating the pluripotency level of stem cells, and investigated its regulatory mechanism. We demonstrated that mice generated from iPS cells have the same physiological functions as that from ES cells but are prone to tumorigenesis. In addition, we tried to derive mammalian haploid stem cells and explored their applications in reproduction, development, and genetic modification. Using genetically modified haploid ES cells we carried out genetic screening in rats and generated transgenic mice and rats, providing important new tools for studying mammalian reproduction and genetics. On the basis of haploid stem cells, we generated world-first mammalian diploid hybrid ES cells of phylogenetically distal species, which will be a valuable tool in studying XCI and genes with functional differences between species. We also generated viable fertile offspring with mouse phES cells after proper imprinting modifications, thus established a novel strategy of generating bimaternal mammals, which is valuable to uncover the function of genomic imprinting, and to improve assisted reproduction in diverse mammalian species. Through collaborations, we also derived functional gametes in vitro, and discovered the positive role of m6A RNA modification in promoting cell reprogramming. In addition, we established genetic modification systems for several species such as mouse, rat, pig, and non-human primate, derived rat ES cell lines with germline-competent, simultaneously generated multiple gene mutations in rat using CRISPR-Cas system.. We also efficiently generated living biallelic vWF-knockout pigs and biallelic p53 gene mutant Cynomolgus monkey through one-stem method, demonstrating the applicability of CRISPR technology to large animals and providing important tools for preparing animal models for human diseases.

  We have isolated and collected hundreds of ES cell lines, adult stem cell lines, and somatic cell lines of different species and different developmental status, including some cell lines from transgenic animals and human stem cell lines from patients with inherited diseases. We also established cloning platforms for mouse, rat, etc., and are producing animal and cell models for human diseases. In the meantime, we are carrying out series of work on pre-clinical research and safety assessment of stem cells for therapeutic cloning and drug screening, to promote the development of stem cell basic research in regenerative medicine.



Mouse generated from iPS cells via tetraploid complementation demonstrated that iPS cells can attain true pluripotency similar to that of ES cells.



Generation of live transgenic mice from androgenetic haploid ES cells not only demonstrated the developmental pluripotency of androgenentic haploids ES cells, but also provides a new tool for quickly producing animal models of recessive traits and for assisted reproduction.



We identified novel functions of microRNAs in regulating the formation of m6A RNA modification, and the positive role of m6A in promoting cell reprogramming. The findings reveal new mechanisms in regulating cell function and cell fate determination.


Generation of mouse-rat allodiploid embryonic stem cells, which will be a valuable tool in studying XCI and genes with functional differences between species

Plain english:
  Generation of bimaternal mice with parthenogenetic haploid embryonic stem cells after proper imprinting modifications, establishing a novel strategy of generating bimaternal mammals

Selected publications:

  1. Li X#, Cui XL#, Wang JQ #, Wang YK, Li YF, Wang LY, Wan HF, Li TD, Feng GH, Shuai L, Li ZK, Gu Q, Hao J, Wang L, Zhao XY, Liu ZH, Wang XJ, Li W*, Zhou Q*. (2016) Generation and Application of Mouse-Rat Allodiploid Embryonic Stem Cells. Cell 164(1–2): 279–292.
  2. Li Z#, Wan H#, Feng G#, Wang L#, He Z, Wang Y, Wang XJ, Li W*, Zhou Q*, Hu B*. (2016) Birth of fertile bimaternal offspring following intracytoplasmic injection of parthenogenetic haploid embryonic stem cells. Cell Res. 26(1):135-138.
  3. Zhou Q#, Wang M#, Yuan Y#, Wang X, Fu R, Wan H, Xie M, Liu M, Guo X, Zheng Y, Feng G, Shi Q, Zhao XY*, Sha J*, Zhou Q* (2016) Complete Meiosis from Embryonic Stem Cell-Derived Germ Cells In Vitro. Cell Stem Cell 18(3):330-340.
  4. Wan HF#, Feng CJ#, Teng F#, Yang SH#, Hu BY, Niu YY, Xiang P, Fang WZ, Ji WZ, LI W*, Zhao XY*, Zhou Q*. One-step generation of p53 gene biallelic mutant Cynomolgus monkey via the CRISPR/Cas system. Cell Research 25(2)(2015):258-261.
  5. Li W#, Li X#, Li TD#, Jiang MG#, Wan HF, Luo GZ, Feng CJ, Cui XL, Teng F, Yuan Y, Zhou Q, Gu Q, Shuai L, Sha JH, Xiao YM, Wang L, Liu ZH, Wang XJ, Zhao XY, Zhou Q*. (2014) Genetic modification and screening in the rat using haploid embryonic stem cells. Cell Stem Cell. 14(3):404-414.
  6. Li W, Teng F, Li TD, Zhou Q*. (2013) Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems. Nat Biotechnol. 31: 684–686
  7. Li W#, Shuai L#, Wan HF#, Dong MZ#, Wang M, Sang LS, Feng CJ, Luo GZ, Li TD, Li X, Wang LB, Zheng QY, Sheng C, Wu HJ, Liu ZH, Liu L, Wang L, Wang XJ, Zhao XY*, Zhou Q*. (2012) Androgenetic haploid embryonic stem cells produce live transgenic mice. Nature. 490(7420):407-411.
  8. Sheng C#, Zheng QY#, Wu JY#, Xu Z, Wang LB, Li W, Zhang HJ, Zhao XY, Liu L, Wang ZW, Guo CL, Wu HJ, Liu ZH, Wang L, He SG, Wang XJ, Chen ZG*, Zhou Q*. (2012) Direct reprogramming of setoli cells into multipotent neural stem cells by defined factors. Cell Res. 22:208-218.
  9. Liu L#, Luo GZ#, Yang W#, Zhao X#, Zheng Q, Lv Z, Li W, Wu HJ, Wang L, Wang XJ*, Zhou Q*. (2010) Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells. J Biol Chem. 285, 19483-19490.
  10. Zhao XY#, Li W#, Lv Z#, Liu L, Tong M, Hai T, Hao J, Guo CL, Ma QW, Wang L, Zeng FY*, Zhou Q*. (2009) iPS cells produce viable mice through tetraploid complementation. Nature 461(7260):86-90.


We identified an imprinted genomic region encoding a cluster of microRNAs, the expression of which is positively correlated with the pluripotency levels of iPS cells, and thus can serve as the molecular marker for evaluating the pluripotency level of stem cells at an early stage.


Mouse Sertoli cells may be directly transdifferentiated into multipotent neural stem cells (NSCs) by defined factors. These induced neural stem cells express normal NSC-specific markers and have the similar global genomic expression profile to that of normal NSCs.


One-step generation of multiple gene mutations in rat and p53 gene biallelic mutant monkey via CRISPR/Cas system.