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Xin Li, Ph.D.

Stem cell biology in tissue regeneration and metastasis
 

　　Our research interests are mainly focused on developmental biology, stem cell biology, cancer stem cells and metastasis. we have accomplished a series of pioneering research in these research areas, including 1, Generating the world's first rat haploid embryonic stem cells and demonstrating their stem cell pluripotency and gametogenic property; 2, Establishing the world's first mouse-rat inter-species allodiploid stem cells and confirming their genome stability and stem cell pluripotency. With this powerful tool, we investigated important scientific issues such as the maintenance of stem cell pluripotency, X chromosome inactivation, and evolutionary differences in gene regulation between species. 3, Report of metabolic abnormal traits in parent mice can be transmitted across generations through sperm and further revealing the mechanism of transgenerational inheritance via sperm tsRNA as a carrier. With these pioneering research efforts, we have published 16 SCI papers, including 9 papers as the first author (including co-first) in top journals such as Cell, Science, and Cell Stem Cell. Our future study will focus on molecular mechanisms of wound-healing microenvironment in regulating stem cell traits during tissue regeneration and cancer metastasis.



Establishment and application of rat haploid ES cells



Establishing the world's first mouse-rat inter-species allodiploid stem cells and confirming their genome stability and stem cell pluripotency. With this powerful tool, we investigated important scientific issues such as the maintenance of stem cell pluripotency, X chromosome inactivation, and evolutionary differences in gene regulation between species.

 

 

Plain English:
Stem cells play key role in the development of the different tissues during morphogenesis and their maintenance during adult life. Stem cells have the unique capacity to self-renew and to differentiate into the different cell lineages that are also critical for regenerating tissue after injuries. We are trying to understand how stem cells give rise to the different tissues. We study how stem cells respond to different signals from their environment and orchestrate the changes in chromatin, transcription, translation, cell polarity, adhesion and cytoskeletal dynamics in normal tissue development, homeostasis, and tissue regeneration. We want to take lesions from the normal process of tissue dynamics to understand how these processes were disrupted or hijacked in aging and cancer. In our research approaches, we will utilize a broad range of techniques encompassing cell, molecular and developmental biology.

 

Selected publications:

  1. Guihai Feng, Xin Qin, Jiahao Zhang, Wuliang Huang, et al., Xin Li*. CellPolaris: Decoding Cell Fate through Generalization Transfer Learning of Gene Regulatory Networks. bioRxiv (2023).
  2. Xiaodong Yang, Guole Liu, Guihai Feng, Dechao Bu, Pengfei Wang, Jie Jiang, et al., Xin Li*. GeneCompass: Deciphering Universal Gene Regulatory Mechanisms with Knowledge-Informed Cross-Species Foundation Model. bioRxiv (2023).
  3. Yun Zhang, Joana Liu Donaher, Sunny Das, Xin Li, et al., Genome-wide CRISPR screen identifies PRC2 and KMT2D-COMPASS as regulators of distinct EMT trajectories that contribute differentially to metastasis. Nat Cell Biol (2022).
  4. Li X, Wang J, Wang L, Gao Y, Feng G, Li G, Zou J, Yu M, Li YF, Liu C, Yuan XW, Zhao L, Ouyang H, Zhu JK, Li W, Zhou Q, Zhang K. Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging. Signal Transduct Target Ther (2022).
  5. Li X, Wang J, Wang L, Feng G, Li G, Yu M, Li Y, Liu C, Yuan X, Zang G, Li Z, Zhao L, Ouyang H, Quan Q, Wang G, Zhang C, Li O, Xiang J, Zhu JK, Li W, Zhou Q, Zhang K. Impaired lipid metabolism by age-dependent DNA methylation alterations accelerates aging. Proc Natl Acad Sci USA (2020).
  6. Xia HM*, Li Xin*, Gao WW*, Fu X, Ronnie H. Fang, Zhang LF, Zhang Kang. Tissue repair and regeneration with endogenous stem cells. Nat Rev Mater (2018). 
  7. Zhang Y*, Zhang X*, Shi J*, Tuorto F*, Li Xin*, Liu Y, Liebers R, Zhang L, Qu Y, Qian J, Pahima M, Liu Y, Yan M, Cao Z, Lei X, Cao Y, Peng H, Liu S, Wang Y, Zheng H, Woolsey R, Quilici D, Zhai Q, Li L, Zhou T, Yan W, Lyko F, Zhang Y, Zhou Q, Duan E, Chen Q. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nature Cell Biology (2018).
  8. Li Xin*, 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*. Generation and application of mouse-rat allodiploid embryonic stem cells. Cell (2016).
  9. Wang JQ*, Li Xin*, Wang L*, Li J, Zhao Y, Bou G, Li Y, Jiao G, Shen X, Wei R, Liu S, Xie B, Lei L, Li W, Zhou Q, Liu Z. A novel long intergenic noncoding RNA indispensable for the cleavage of mouse two-cell embryos. EMBO Rep (2016).
  10. Chen Q*, Yan M*, Cao Z*, Li Xin*, Zhang Y*, Shi J*, Feng GH, 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).
  11. Li Xin*, Wang J.*, Wang L.*, Wan H., Li Y., Li TD., Wang Y., Shuai L., Mao Y., Cui X., Wang L., Liu Z., Zhou Q. Co-participation of paternal and maternal genomes before blastocyst stage is not required for full-term development of mouse embryos. Journal of Molecular Cell Biology (2015).
  12. Wang J*, Li Xin*, Zhao Y., Li J., Zhou Q., and Liu Z. (2015). Generation of cell-type-specific gene mutations by expressing the sgRNA of the CRISPR system from the RNA polymerase II promoters. Protein & cell (2015).
  13. Shi J.*, Chen Q.*, Li Xin*, 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).
  14. Li Wei*, Li Xin*, Li TD*, Jiang MG*, Wan H, Luo GZ, Feng C, Cui X, Teng F, Yuan Y, Zhou Q, Gu Q, Shuai L, Sha J, Xiao Y, Wang L, Liu Z, Wang XJ, Zhao XY, Zhou Q. Genetic modification and screening in rat using haploid embryonic stem cells. Cell Stem Cell (2014).
  15. Li Xin*, Xia BL*, Li W, Zhou Q. Assessing reprogramming by chimera formation and Tetraploid complementation. Methods Mol Biol (2014).