We aim to understand the unique property of germ cells. Germ cells are the only cell type whose lifespan is not limited as they are reprogrammed with totipotency in the next generation. To ensure the sustainability of a species, germ cells need to fulfill three additional new properties that are distinct from any other cell type.
First, the germ cells must faithfully replicate their genome, avoiding invasion from foreign genetic elements, and only recognizing gametes from their own species to fertilize.
Second, the germ cells need to diversify their offspring. Mutations primarily come from meiotic recombination, transposon insertions/deletions, and spontaneous point mutations and structural variations. It has been found that the number of mutations increases with age in men.
Third, some acquired traits are inheritable. Although once discredited, Lamarkian inheritance has been resurrected by recent advances in our understanding of epigenetics. It has been shown that germ cells are sensitive to the environment & can pass epigenetic information across generations.
We want to understand the basic principles underlying these unique properties from two specific angles. The first is through an RNA biology oriented approach. We strive to understand how various germ-line RNAs prepare and shape epigenetic information flowing across generations. The second focuses on comparative biology. We have established alternative model organisms, such as chickens and lizards, for studying germ cell biology. We are adopting an interdisciplinary approach that includes genetics, epigenetics, cell biology, RNA biochemistry, reproductive biology, early embryology, evolutionary biology, and bioinformatics. Currently, our ongoing projects are centered on two related topics: PIWI-interacting RNAs (piRNAs) and sperm RNAs. piRNAs are a recently discovered type of small RNA that offers great promise in advancing our understanding of germ cell biology, whereas sperm RNAs may offer important insight into the transgenerational flow of epigenetic information. Finally, beyond infertility and contraception, what we have learned in germ cells can be applied to other cell types to promote regeneration or anti-aging. At the same time, understanding the mis-activation of some germline properties can offer insight into some diseases, such as cancer.
- Sun, Y.H., Zhu, J., Xie, L.H., Li, Z., Meduri, R., Zhu, X., Song, C., Ricci, E.P., Weng, Z., and Li, X.Z. Ribosomes guide pachytene piRNA formation on long intergenic piRNA precursors. Nature Cell Biology, 2020: 1-13
- Li, X.Z. What can piRNA research learn from chickens, and vice versa? Canadian Journal of Animal Science, 2019, ja
- Sun, Y.H., Jiang F., and Li, X.Z. Disruption of Tdrd5 decouples the stepwise processing of long precursor transcripts during pachytene piRNA biogenesis.Biology of Reproduction, 2018. ioy110
- Sun, Y.H., Xie, L.H., Zhuo, X., Chen, Q., Ghoneim, D., Zhang, B., Jagne, J., Yang, C., and Li, X.Z. Domestic chickens activate a piRNA defense against avian leukosis virus. ELife, 2017. Apr 6;6. PMID: 28384097
- Sharma, U., Conine, C.C., Shea, J.M., Boskovic, A., Derr, A.G., Bing, X.Y., Belleannee, C., Kucukural, A., Serra, R.W., Sun, F., Song, L., Carone, B.R., Ricci, E.P., Li, X.Z., Fauquier, L., Moore, M.J., Sullivan, R., Mello, C.C., Garber, M., and Rando O.J. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science, aad6780
- Ishiguro, K., Kim, J., Shibuya, H., Hernández-Hernández, A., Suzuki, A., Fukagawa, T., Shioi, G., Kiyonari, H., Li, X.C., Schimenti, J., Höög, C., and Watanabe Y. Meiosis-specific cohesin mediates homolog recognition in mouse spermatocytes. Genes & Development, 28(6):594-607, 2014 PMID:24589552
- Moran, Y., Fredman, D., Praher D., Li, X.Z., Wee, L., Rentzsch, F., Zamore, P.D., Technau, U. and Seitz, H. Cnidarian microRNAs frequently regulate targets by cleavage. Genome Research, 24(4):651-63, 2014 PMID:24642861
- Li, X.Z., Roy, C.K., Dong, X., Bolcun-Filas, E.M., Wang, J., Han, B.W., Xu, J., Moore, M.J., Schimenti, J.C., Weng Z., and Zamore, P.D. An Ancient Transcription Factor Initiates the Burst of piRNA Production During Early Meiosis in Mouse Testes. Molecular Cell, 50: 67-81, 2013 PMID: 23523368
- Li, X.C., Bolcun-Filas, E.M. and Schimenti, J.C. Genetic evidence that synaptonemal complex axial elements govern recombination partner choice in mice. Genetics, 189: 71-82, 2011PMID: 21750255
- Li, X.C. and Tye, B.K. Ploidy Dictates Repair Pathway Choice under DNA Replication Stress. Genetics, 187: 1031-40, 2011 PMID: 21242538
- Li, X.C., Schimenti, J.C. and Tye, B.K. Aneuploidy and Improved Growth are Coincident but Not Causal in a Yeast Cancer Model. PLOS Biology l 7: e1000161, 2009 PMCID: PMC2708349
- Li, X.C., Barringer, B.C. and Barbash, D.A. The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility. Heredity 9: 1-7, 2008 PMID: 18766201
- Li, X.C. and Schimenti, J.C. Mouse pachytene checkpoint 2 (Trip13) is required for completing meiotic recombination but not synapsis. PLOS Genetics 3: 1785-1785, 2007 PMCID: PMC1941754
- Chen, F., Chen, Y., Dong, Y., Li, X., Xu, M., Zhang, C., Yan, Y., and Zhang, G. OsDof28, a New Member of the DOF Transcription Factor Family from Rice. Tsinghua Science and Technology 10: 454-460, 2005
- Li, X., Jia, S., Jian, J., Lin, M., Li, Q., Huang, X., Zhang, C., Zhang, R., and Zhang, G. Physiological Defense Mechanism of Ligularia intermedia Against UV-B Radiation on Dongling Mountain. Tsinghua Science and Technology 8: 481-486, 2003