Bo Xia
“The joy of discovery is certainly the liveliest that the mind of man can ever feel”
-Claude Bernard-
Single-cell and spatial transcriptomics >>
Nature built a Lego castle, and we are dismantling it to understand how it was built.
With recent advances in single-cell sequencing technologies and methods, life science has entered an era of 'Single-Cell Omics'. Working in the Yanai lab allows me to use these cutting-edge technologies to understand the biological process to an unprecedented level. Recently, we used single-cell RNA-seq to understand mammalian spermatogenesis. Our work clearly characterized the transcriptomic dynamics during spermatogenesis. We continued the study to understand the gene expression network from mitotic amplification to meiosis and finally to the maturation of sperm cells. Beyond that, I will constantly use and develop novel technologies to revolutionize our understanding of complex biological problems and disease systems.
<< Genome Evolution
Mutations are roughly random, but evolution is not.
Mutations must be inherited to the next generation so that to spread out among the population. We study the mutation pattern in the germ cells so that to understand the human genome evolution. We explore how gene expression in human male germ cells affects mutation rates. Very excitedly, we find that the widespread gene expression in male germ cells modulates gene mutation rates, which we termed 'transcriptional scanning'. Such a biased mutation pattern ultimately shapes gene evolution rates. We want to continue this study and expand this principle to other systems, including neurodegenerative diseases and tumor genome evolution.
Epigenetics and chemical biology >>
Sometimes a small chemistry makes a big difference in biology.
Chemical modifications modulate various biological processes. DNA methylation (5mC) and TET-protein-mediated DNA methylation-derivatives (5hmC, 5fC and 5caC) represent one major part of epigenetics. The critical information to understand the function of an epigenetic factor is to profile its genome-wide distribution pattern. Before coming to NYU Langone, I worked with Dr. Chengqi Yi and we developed several unique and robust chemical methods to analyze the genome distribution map of 5fC and 5hmC. Represented by 'fC-CET' and 'CLEVER-seq', these methods benchmarked the concept of 'bisulfite-free and base-resolution'. We used these methods to analyze the epigenomes in embryonic stem cells and even in single cells of the early developing embryo. These technologies will help us understand the molecular basis of epigenetic gene expression regulation and how these chemical modifications affect mammalian development.
PUBLICATIONS
SELECTED PUBLICATIONS:
Xia B.#, Zhang W., Wudzinska A., Huang E., Brosh R., Pour M., Miller A., Dasen J., Maurano M., Kim S., Boeke J.#, and Yanai I.# (2021) The genetic basis of tail-loss evolution in humans and apes. BioRxiv. (co-corresponding author)
News: New York Times, Science, New Scientist, The Scientist, Smithsonian Magazine, BBC News, Mashable
Tan, J., Rodriguez-Hernaez, J., Sakellaropoulos, T., Boccalatte, F., Aifantis, I., Skok, J., Fenyo, D., Xia B.#, Tsirigos, A.# (2022) Cell type-specific prediction of 3D chromatin architecture. BioRxiv. (co-corresponding author)
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Xia B, Yan Y, Baron M, Wagner F, Barkley D, Chiodin M, Kim SY,
Keefe DL, Alukal JP, Boeke JD and Yanai I. Widespread transcriptional
scanning in the testis modulates gene evolution rates. Cell 180 (2), 248-262.
Preview: Sperm Go to (Transcription) Extremes
News: EurekaAlert!, ScienceDaily, Yahoo! News, Phys.org,
News Medical Life Sciences, Labroots, BioArt, 奇点网
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Xia B and Yanai I. (2019) A periodic table of cell types. Development,
146(12): dev169854.
Zhu C*, Gao Y*, Guo H*, Xia B*, Song J, Wu X, Zeng H, Kee K, Tang F# and Yi C# (2017) Single-Cell 5-Formylcytosine Landscapes of Mammalian Early Embryos and ESCs at Single-Base Resolution. Cell Stem Cell, 20(5), 720-731.
Xia B*, Han D*, Lu X*, Sun Z, Zhou A, Yin Q, Zeng H, Liu M, Jiang X, Xie W, He C# and Yi C# (2015) Bisulfite-free, base-resolution analysis of 5-formylcytosine at the genome scale. Nature Methods, 12(11), 1047–1050.
* indicates co-first authors
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PATENTS:
Yi C, Xia B, Zhou A. 5-formylcytosine specific chemical labeling methods and related applications. Priority date: 2013-09-27. Granted: WO2015043493A1 (2015); CN104311618B (2015); JP6243013B2 (2017); EP3061764B1 (2019); US10519184B2 (2019). (Commercialized)
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Yi C, Zhu C, Xia B. 5-formylcytosine labeling methods and applications in single-base resolution sequencing. Priority date: 2017-02-28. Granted: WO2018157775A1 (2017); CN106957350B (2019). (Commercialized)
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SCIENCE OUTREACH:
Xia B. How to turn a Eureka moment into a research project: from ‘napkin idea’ to published paper. (2020) Nature Index.
Xia B. Eureka! My path to studying the epigenome. (2018) Journal of Stories in Science, #95: 1-3.
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OTHER PUBLICATIONS:
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Xia B. and Yanai, I (2021) Gene expression levels tune germline mutation rates through the compound effects of transcription-coupled repair and damage. Human Genetics, online
Zeng H*, Song R*, Mondal M*, Zhang J, Xia B, Liu M, Zhu C, He B, Gao Y#, and Yi C#. (2019) Unnatural cytosine bases recognized as thymines by DNA polymerases via a tautomerization-dependent mechanism. Angewandte Chemie. 131(1), 136-139.
Zeng H*, He B*, Xia B, Bai D, Lu X, Cai J, Chen L, Zhou A, Zhu C, Gao Y, Guo H, Meng H, He C#, Dai Q# and Yi C#. (2018) Bisulfite-free, nano-scale analysis of 5-hydroxymethylcytosine at single base resolution. Journal of the American Chemical Society, 140(41), 13190–13194.
Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, Ng V, Xia B, Witkowski M, Mitchell-Flack M, Grillo I, Bakogianni S, Ndiaye-Lobry D, Martín M, Guillamot M, Banh R, Xu M, Figueroa M, Dickins R, Abdel-Wahab O, Park C, Tsirigos A, Neel B# and Aifantis I# (2017). Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cell, 170(6), 1079-1095.
Peng J, Xia B and Yi C. (2016) Single-base resolution analysis of DNA epigenome via high-throughput sequencing. Science China Life Sciences, 59(3), 219–226.
Lu L, Zhu C, Xia B and Yi C. (2014) Oxidative demethylation of DNA and RNA mediated by non-heme iron-dependent dioxygenases. Chemistry–An Asian Journal, 9(8): 2018–2029.
Xia B, Sun Y, Sun X, Liu Q and Wang B. (2012) Study on the difference of Amata emma’s preference to cloth in six different colors. Chinese Agricultural Science Bulletin, 28(36): 255-258.
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Xia B, Sun X, Sun Y and Wang B. (2012) Study on the difference of phototaxis insects’ preference to cloth in different colors. Journal of Anhui Agricultural Sciences, 40(19): 10119-10121.
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