General

Huayu Qi, Ph. D.

Principal Investigator

Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences

Address: 190 Kaiyuan Blvd., A303, Science City, Huangpu District, Guangzhou, Guangdong, China 510630

E-mail: qi_huayu@gibh.ac.cn; 

Office Phone: 020-32015264

Research Areas

      Germ cells play vital functions during animal development and evolution.  Both male and female germ cells participate in the propagation of genetic information from generation to generation and the maintenance of animal species.  Research on germ cells can thus not only provide answers to fundamental scientific questions but also help to solve social problems that are relevant to health and medicine, including treatment of reproductive and genetic diseases, improvement of reproductive health, regulation of birth rate and population control, development of new strategies for drug discovery among other clinical applications.  Thorough understanding of germ cells and their medical applications require systemic research on the molecular mechanisms that regulate the development and function of germ cells.  
      Following the birth of the animal, male germline stem cells undergo a series of complicated events, including mitosis, meiosis and cellular morphogenesis, eventually give rise to matured spermatozoa.  It takes about 35 days in mouse and 60 days in human to complete the process.  Sexually matured male animals can produce sperm continuously throughout their lives.  This is mainly due to their robust stem cell system, the spermatogonial stem cells (SSCs) that undergo continuous self-renewal and differentiation.  Although several genes and signaling pathways have been shown to be important for the regulation of mouse SSCs from research over past decades, much remain to be explored.  Once complete meiotic cell division, haploid spermatids undergo spermiogenesis, a cellular morphogenetic process of which we understand little.  Using mouse as a model system, we wish to understand the molecular mechanisms that govern mammalian spermatogenesis: what are the determining factors that regulate the developmental program of male germ cells and how do they work?
      Questions that need to be addressed included: what are the key factors and molecular mechanisms that regulate the self-renewal and differentiation of male germline stem cells and how are the differentiation and growth of male germ cells regulated in mouse?  Answers to these questions will not only enable us to decipher the regulation of mammalian male germ cells, but also shed light on our understanding of more general questions, such as stem cell biology, cellular ageing and the genetic etiology of human diseases.
 
Current Research:
1) Regulation of self-renewal and differentiation of spermatogonial stem cells (SSCs).  Mouse spermatogonial stem cells support the life-long generation of male gamete – sperm.  Although not as well studied as the germline stem cells in lower species, such as Drosophila, mouse SSCs have been an ideal model system for the study of stem cell biology and germ cell development in mammals for decades.  However, many questions remain to be fully addressed.  What are the molecular signatures of mammalian SSCs?  How are their pluripotency maintained by signals emitted from specific “niche” environment during their self-renewal and proliferation?  Using transgenic mouse model, we purified mouse SSCs from post-natal mice and analyzed their global gene expression profiles during development.  These comparative gene expression studies suggested that changes in global gene expression occur during the establishment of SSCs (from their precursor cells – gonocytes) and differentiation (towards differentiated spermatogenic cells).  Numerous genes are highly enriched in SSCs, comparing to the gonocytes and differentiated spermatogenic cells, including spermatocytes and spermatids.  Using mouse genetics, biochemical and cell biological approaches, including in situ hybridization and in vitro cell culture, we are continuing the analyses of SSC-specific gene expression patterns, as well as the biological functions of these genes.  We are particularly interested in the SSC-enriched RNA binding proteins (RBPs) and their involvement in the post-transcriptional and translational regulation during the self-renewal and proliferation of mouse spermatogonial stem cells.  
2) Post-transcriptional regulation of sperm-specific gene expression during mouse spermiogenesis.  Spermatogenesis in mouse encompassing three consecutive stages: mitosis, meiosis and cell morphogenesis.  The last stage, also called spermiogenesis, occurs when spermatocytes complete meiosis and enter the post-meiotic development during which round, haploid spermatids are transformed into mature, whip-like spermatozoa with biological functions.  The morphogenesis of spermatids includes numerous cellular changes such as nuclear condensation, acrosome formation and flagella formation.  This process is regulated on both transcriptional and translational levels.  Due to the chromatin structure changes and nuclear condensation, haploid spermatids have limited gene transcription activity.  Proteins required for the cellular morphogenesis are synthesized from both pre-stored and newly made messengers.  The post-transcriptional and translational regulations are thus the main regulatory mechanisms that govern the final stage of the development of spermatozoa.  Through the analyses of sperm-specific protein AKAP3 (Protein kinase A anchoring protein 3), we found that multiple RNA binding proteins and PKA signaling pathway play important roles in regulating gene expression during spermiogenesis.  RNA binding protein complex(es) and PKA signaling may participate in the regulation of messenger RNAs and influence their translational activities in response to environmental stimuli during the elongating stage of spermiogenesis.  Combining biochemical, cellular and molecular approaches, we are dissecting the relationships among the RNA binding proteins and mechanisms by which signaling pathways participate in the cellular morphogenesis of sperm.
3) Cell fate determination during mouse early embryogenesis.  

One of the highly debated questions in stem cell and developmental biology is that how the cell fate of a particular cell type (like germ cells) is determined at the earliest time of embryonic development in mammals.  Germ cells are among the first cell lineages that are specialized during early development.  In lower species, including Drosophila and C. elegans,  they are determined during as early as the first cell division by maternal factors inherited from female germ cells – the eggs.  However, it is not clear how cell fate determination is regulated during mammalian early embryogenesis.  We are conducting experiments with mouse pre-implantation embryos to dissect the molecular and physiological differences among early embryonic cells in order to understand how the first cell fate decisions are come about in mammals.

Education

B.Sc.  Western Kentucky University                                     

Ph.D.  Mount Sinai School of Medicine, New York


Experience

Principal Investigator at South China Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (2007 – present).  Dr. Qi received his Ph.D. from Mount Sinai School of Medicine, New York.  He joined Guangzhou Institutes of Biomedicine and Health following the post-doctoral research at Children’s Hospital Boston, Harvard Medical School.  His work on cellular mechanism of species-specific sperm receptor, the zona pellucida glycoprotein synthesis and assembly, as well as the regulation of sperm motility during fertilization have been published in journals including Molecular Biology of the Cell, Nature Cell Biology and Proceedings of National Academy of Science, USA.  His recent work on mouse spermatogenesis has led him to unveil uncharacterized genes and regulatory networks that play important functions during self-renewal and proliferation of male germline stem cells, as well as in the process of post-meiotic development of male gamete.

Publications

Selected Publications:

  • Guo, Y., Yang, L. and Qi, H.  Transcriptome analysis of mouse male germline stem cells reveals characteristics of mature spermatogonial stem cells.  Yi Chuan Jul 20; 44(7): 591-608 (2022).  DOI: 10.16288/j/yczz.22-047.
  • Zou, Q., Yang, L. and Qi, H.  Protocol for isolation and proteostatic analysis of sub-populations of spermatogenic cells in mouse.  STAR Protocols May 14; 3(2): 101398 (2022).  DOI: 10.1016/j.xpro.2022.101398.

  • Shi, K., Yang, L., Zhuang, X., Zhang, L. and Qi, H.  Yeast Two-Hybrid Screen Identifies PKA-Rialpha Interacting Proteins during Mouse Spermiogenesis.  Genes (Basel) Nov 30; 12(12): 1941 (2021).  DOI: 10.3390/genes12121941.

  • Zou, Q., Yang, L., Shi, R., Qi, Y., Zhang, X. and Qi, H.  Proteostasis regulated by testis-specific ribosomal protein RPL39L maintains mouse spermatogenesis.  iScience Oct 30; 24(12): 103396 (2021).  DOI: 10.1016/j.isci.2021.103396.

  • Zou, Q. and Qi, H.  Deletion of ribosomal paralogs Rpl39 and Rpl39l compromises cell proliferation via protein synthesis and mitochondrial activity.  International Journal of Biochemistry and Cell Biology Oct; 139: 106070 (2021).  DOI: 10.1016/j.biocel.2021.106070.

  • Xu, K., Yang, L., Zhang, L. and Qi, H.  Lack of AKAP3 disrupts integrity of sub-cellular structure and proteome of mouse sperm and causes male sterility.  Development 147(2): dev18107.  doi:10.1242/dev.181057, 2020.

  • Wu, Y., Xu, K. and Qi, H.  Domain-functional analyses of PIWIL1 and PABPC1 indicate their synergistic roles in protein translation via 3’-UTRs of meiotic mRNAs.  Biology of Reproduction 99(4): 773-788, 2018.
  • Qi, H. RNA-binding proteins in mouse male germline stem cells: a mammalian perspective. Cell Regen (Lond) 5: 1, 2016.
  • Zheng, Z., Li H., Zhang, Q., Yang, L. and Qi, H. Unequal distribution of 16S mtrRNA at the 2-cell stage regulates cell lineage allocations in mouse embryos. Reproduction 151(4): 351-367, 2016.
  • Xu, K., Qi, H. Sperm specific AKAP3 is a dual specificity anchoring protein that interacts with both protein kinase A regulatory subunits via conserved N-terminal amphipathic peptides. Molecular Reproduction and Development, 81(7): 595-607, 2014.
  • Xu, K., Yang, L., Zhao, D., Wu, Y., Qi, H. AKAP3 synthesis is mediated by RNA binding proteins and PKA signalling during mouse spermiogenesis. Biology of Reproduction, 90(6): 1-14, 2014.
  • Sun, R., Qi, H. Dynamic expression of combinatorial replication-dependent histone variant genes during mouse spermatogenesis. Gene Expression Patterns, 14(1): 30-41, 2013.
  • Yang, L., Wu, W., Qi, H.  Gene expression profiling revealed specific spermaogonial stem cell genes in mouse. Genesis, 51:2:83-96, 2013.