Education

Medical School
Peking University Health Science Center, Beijing, China
Graduate School
University of Utah, Salt Lake City, Utah (Neurobiology and Anatomy)
Fellowship
National Institute on Aging, National Institutes of Health

Areas of Interest

Research Interests

My research focuses on using human induced pluripotent stem cells (iPSCs) to model central nervous system (CNS) development and disease. Specifically, by differentiating and genetically manipulating iPSCs with cutting edge genome editing tools such as CRISPR-mediated gene targeting, we are trying to dissect the developmental pathways and the corresponding pathogenesis in the glial lineage. My long-term goal is to identify therapeutic targets for the treatment of CNS injury and neurodegenerative diseases.

Publications

Publication Information

PUBLICATIONS:

  1. Liu, Y., Virshup, D. M., White, R. L., and Hsu, L. C. (2002). Regulation of BRCA1 phosphorylation by interaction with protein phosphatase 1alpha. Cancer Res 62, 6357-6361.
  2. Liu, Y., Wu, Y., Lee, J. C., Xue, H., Pevny, L. H., Kaprielian, Z., and Rao, M. S. (2002). Oligodendrocyte and astrocyte development in rodents: an in situ and immunohistological analysis during embryonic development. Glia 40, 25-43.
  3. Luo, Y., Cai, J., Liu, Y., Xue, H., Chrest, F. J., Wersto, R. P., and Rao, M. (2002). Microarray analysis of selected genes in neural stem and progenitor cells. J Neurochem 83, 1481-1497.
  4. Mayer-Proschel, M., Liu, Y., Xue, H., Wu, Y., Carpenter, M. K., and Rao, M. S. (2002). Human neural precursor cells – an in vitro characterization. Clin Neurosci Res 2, 58-69.
  5. Lee, J., Wu, Y., Qi, Y., Xue, H., Liu, Y., Scheel, D., German, M., Qiu, M., Guillemot, F., Rao, M., and Gradwohl, G. (2003). Neurogenin3 participates in gliogenesis in the developing vertebrate spinal cord. Dev Biol 253, 84-98.
  6. Liu, Y., and Rao, M. (2003). Oligodendrocytes, GRPs and MNOPs. Trends Neurosci 26, 410-412.
  7. Liu, Y., and Rao, M. S. (2003). Transdifferentiation–fact or artifact. J Cell Biochem 88, 29-40.
  8. Wu, Y., Liu, Y., Levine, E. M., and Rao, M. S. (2003). Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors. Dev Dyn 226, 675-689.
  9. Brimble, S. N., Zeng, X., Weiler, D. A., Luo, Y., Liu, Y., Lyons, I. G., Freed, W. J., Robins, A. J., Rao, M. S., and Schulz, T. C. (2004). Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001. Stem Cells Dev 13, 585-597.
  10. Han, S. S., Liu, Y., Tyler-Polsz, C., Rao, M. S., and Fischer, I. (2004). Transplantation of glial-restricted precursor cells into the adult spinal cord: survival, glial-specific differentiation, and preferential migration in white matter. Glia 45, 1-16.
  11. Liu, Y., Han, S. S., Wu, Y., Tuohy, T. M., Xue, H., Cai, J., Back, S. A., Sherman, L. S., Fischer, I., and Rao, M. S. (2004). CD44 expression identifies astrocyte-restricted precursor cells. Dev Biol 276, 31-46.
  12. Liu, Y., and Rao, M. S. (2004). Glial progenitors in the CNS and possible lineage relationships among them. Biol Cell 96, 279-290.
  13. Liu, Y., and Rao, M. S. (2004). Olig genes are expressed in a heterogeneous population of precursor cells in the developing spinal cord. Glia 45, 67-74.
  14. Tuohy, T. M., Wallingford, N., Liu, Y., Chan, F. H., Rizvi, T., Xing, R., Bebo, B., Rao, M. S., and Sherman, L. S. (2004). CD44 overexpression by oligodendrocytes: a novel mouse model of inflammation-independent demyelination and dysmyelination. Glia 47, 335-345.
  15. Zeng, X., Chen, J., Liu, Y., Luo, Y., Schulz, T. C., Robins, A. J., Rao, M. S., and Freed, W. J. (2004). BG01V: a variant human embryonic stem cell line which exhibits rapid growth after passaging and reliable dopaminergic differentiation. Restor Neurol Neurosci 22, 421-428.
  16. Back, S. A., Tuohy, T. M., Chen, H., Wallingford, N., Craig, A., Struve, J., Luo, N. L., Banine, F., Liu, Y., Chang, A., Trapp, B. D., Bebo, B. F., Jr., Rao, M. S., and Sherman, L. S. (2005). Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nat Med 11, 966-972.
  17. Maitra, A., Arking, D. E., Shivapurkar, N., Ikeda, M., Stastny, V., Kassauei, K., Sui, G., Cutler, D. J., Liu, Y., Brimble, S. N., Noaksson, K., Hyllner, J., Schulz, T. C., Zeng, X., Freed, W. J., Crook, J., Abraham, S., Colman, A., Sartipy, P., Matsui, S., Carpenter, M., Gazdar, A. F., Rao, M., and Chakravarti, A. (2005). Genomic alterations in cultured human embryonic stem cells. Nat Genet 37, 1099-1103.
  18. Talbott, J. F., Loy, D. N., Liu, Y., Qiu, M. S., Bunge, M. B., Rao, M. S., and Whittemore, S. R. (2005). Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes. Exp Neurol 192, 11-24.
  19. Bibikova, M., Chudin, E., Wu, B., Zhou, L., Garcia, E. W., Liu, Y., Shin, S., Plaia, T. W., Auerbach, J. M., Arking, D. E., Gonzalez, R., Crook, J., Davidson, B., Schulz, T. C., Robins, A., Khanna, A., Sartipy, P., Hyllner, J., Vanguri, P., Savant-Bhonsale, S., Smith, A. K., Chakravarti, A., Maitra, A., Rao, M., Barker, D. L., Loring, J. F., and Fan, J. B. (2006). Human embryonic stem cells have a unique epigenetic signature. Genome Res 16, 1075-1083.
  20. Cai, J., Chen, J., Liu, Y., Miura, T., Luo, Y., Loring, J. F., Freed, W. J., Rao, M. S., and Zeng, X. (2006). Assessing self-renewal and differentiation in human embryonic stem cell lines. Stem Cells 24, 516-530.
  21. Cai, J., Shin, S., Wright, L., Liu, Y., Zhou, D., Xue, H., Khrebtukova, I., Mattson, M. P., Svendsen, C. N., and Rao, M. S. (2006). Massively parallel signature sequencing profiling of fetal human neural precursor cells. Stem Cells Dev 15, 232-244.
  22. Josephson, R., Sykes, G., Liu, Y., Ording, C., Xu, W., Zeng, X., Shin, S., Loring, J., Maitra, A., Rao, M. S., and Auerbach, J. M. (2006). A molecular scheme for improved characterization of human embryonic stem cell lines. BMC Biol 4, 28.
  23. Lepore, A. C., Neuhuber, B., Connors, T. M., Han, S. S., Liu, Y., Daniels, M. P., Rao, M. S., and Fischer, I. (2006). Long-term fate of neural precursor cells following transplantation into developing and adult CNS. Neuroscience 142, 287-304.
  24. Liu, Y., Shin, S., Zeng, X., Zhan, M., Gonzalez, R., Mueller, F. J., Schwartz, C. M., Xue, H., Li, H., Baker, S. C., Chudin, E., Barker, D. L., McDaniel, T. K., Oeser, S., Loring, J. F., Mattson, M. P., and Rao, M. S. (2006). Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines. BMC Dev Biol 6, 20.
  25. Li, H., Liu, Y. (co-first author), Shin, S., Sun, Y., Loring, J. F., Mattson, M. P., Rao, M. S., and Zhan, M. (2006). Transcriptome coexpression map of human embryonic stem cells. BMC Genomics 7, 103.
  26. Matsumoto, S., Banine, F., Struve, J., Xing, R., Adams, C., Liu, Y., Metzger, D., Chambon, P., Rao, M. S., and Sherman, L. S. (2006). Brg1 is required for murine neural stem cell maintenance and gliogenesis. Dev Biol 289, 372-383.
  27. Plaia, T. W., Josephson, R., Liu, Y., Zeng, X., Ording, C., Toumadje, A., Brimble, S. N., Sherrer, E. S., Uhl, E. W., Freed, W. J., Schulz, T. C., Maitra, A., Rao, M. S., and Auerbach, J. M. (2006). Characterization of a new NIH-registered variant human embryonic stem cell line, BG01V: a tool for human embryonic stem cell research. Stem Cells 24, 531-546.
  28. Zeng, X., Chen, J., Deng, X., Liu, Y., Rao, M. S., Cadet, J. L., and Freed, W. J. (2006). An in vitro model of human dopaminergic neurons derived from embryonic stem cells: MPP+ toxicity and GDNF neuroprotection. Neuropsychopharmacology 31, 2708-2715.
  29. Josephson, R., Ording, C. J., Liu, Y., Shin, S., Lakshmipathy, U., Toumadje, A., Love, B., Chesnut, J. D., Andrews, P. W., Rao, M. S., and Auerbach, J. M. (2007). Qualification of Embryonal Carcinoma 2102Ep As a Reference for Human Embryonic Stem Cell Research. Stem Cells 25, 437-446.
  30. Schulz, T. C., Swistowska, A. M., Liu, Y., Swistowski, A., Palmarini, G., Brimble, S. N., Sherrer, E., Robins, A. J., Rao, M. S., and Zeng, X. (2007). A large-scale proteomic analysis of human embryonic stem cells. BMC Genomics 8, 478.
  31. Shin, S., Sun, Y., Liu, Y., Khaner, H., Svant, S., Cai, J., Xu, Q. X., Davidson, B. P., Stice, S. L., Smith, A. K., Goldman, S. A., Reubinoff, B. E., Zhan, M., Rao, M. S., and Chesnut, J. D. (2007). Whole genome analysis of human neural stem cells derived from embryonic stem cells and stem and progenitor cells isolated from fetal tissue. Stem Cells 25, 1298-1306.
  32. Sun, Y., Li, H., Liu, Y., Shin, S., Mattson, M. P., Rao, M. S., and Zhan, M. (2007). Cross-species transcriptional profiles establish a functional portrait of embryonic stem cells. Genomics 89, 22-35.
  33. Maynard, S., Swistowska, A. M., Lee, J. W., Liu, Y., Liu, S. T., Da Cruz, A. B., Rao, M., de Souza-Pinto, N. C., Zeng, X., and Bohr, V. A. (2008). Human embryonic stem cells have enhanced repair of multiple forms of DNA damage. Stem Cells 26, 2266-2274.
  34. Magnus, T., Liu, Y., Parker, G. C., and Rao, M. S. (2008). Stem cell myths. Philos Trans R Soc Lond B Biol Sci 363, 9-22.
  35. Sun, Y., Li, H., Liu, Y., Mattson, M. P., Rao, M. S., and Zhan, M. (2008). Evolutionarily conserved transcriptional co-expression guiding embryonic stem cell differentiation. PLoS ONE 3, e3406.
  36. Thyagarajan, B., Liu, Y., Shin, S., Lakshmipathy, U., Scheyhing, K., Xue, H., Ellerstrom, C., Strehl, R., Hyllner, J., Rao, M. S., and Chesnut, J. D. (2008). Creation of engineered human embryonic stem cell lines using phiC31 integrase. Stem Cells 26, 119-126.
  37. Campanelli, J. T., Sandrock, R. W., Wheatley, W., Xue, H., Zheng, J., Liang, F., Chesnut, J. D., Zhan, M., Rao, M. S., and Liu, Y. (2008). Expression profiling of human glial precursors. BMC Dev Biol 8, 102.
  38. Liu, Y., Thyagarajan, B., Lakshmipathy, U., Xue, H., Lieu, P., Fontes, A., MacArthur, C. C., Scheyhing, K., Rao, M. S., and Chesnut, J. D. (2009). Generation of a platform human embryonic stem cell line that allows efficient targeting at a predetermined genomic location. Stem Cells Dev 18, 1459-1472
  39. Xue, H., Wu, S., Papadeas, S., Spusta, S., Swistowska, A. M., MacArthur, C. C., Mattson, M. P., Maragakis, N. J., Capecchi, M., Rao, M. S., Zeng, X., and Liu, Y. (2009). A targeted neuroglial reporter line generated by homologous recombination in human embryonic stem cells. Stem Cells, 27, 1836-1846
  40. Han, Y., Miller, A., Mangada, J., Liu, Y., Swistowski, A., Zhan, M., Rao, M.S., and Zeng, X. Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 4:e7155
  41. Swistowska, AM., da Cruz, AB., Han, Y., Swistowski, A., Liu, Y., Shin, S., Zhan, M., Rao, M.S., and Zeng X. (2010). Stage-specific role for shh in dopaminergic differentiation of human embryonic stem cells induced by stromal cells. Stem Cells Dev 19:71-82
  42. MacArthur, C. C., Xue, H., Van Hoof, D., Lieu, P., Dudas, M., Fontes, A., Andrzej Swistowski, A., Seerke, R., German, M.S., Zeng X., Rao, M. S., Lakshmipathy, U., Chesnut, J. D., and Liu, Y. (2011). Chromatin insulator elements block transgene silencing in engineered hESC lines. Stem Cells Dev Aug 4 [Epub ahead of print].
  43. Liu, Y., Jiang, P., and Deng, W. (2011) Olig gene targeting in human pluripotent stem cells for motor neuron and oligodendrocyte differentiation. Nat Prot 6(5):640-655
  44. Lehmann, H.C., Chen, W, Mi, R., .Wang, S., Liu, Y., Rao, M., Hoke, A. (2012) Human Schwann cells retain essential phenotype characteristics after immortalization. Stem Cells Dev 21:423-431
  45. Wang, Y.C., Nakagawa, M., Garitaonandia, I., Slavin, I., Altun, G., Lacharite, R.M., Nazor, K.L., Tran, H.T., Lynch, C.L., Leonardo, T.R., Liu, Y., Peterson, S. E., Laurent, L. C., Yamanaka, S., Loring, J. F.. (2011). Specific lectin biomarkers for isolation of human pluripotent stem cells identified through array-based glycomic analysis. Cell Res. 2011 Nov;21(11):1551-63. doi: 10.1038/cr.2011.148. Epub 2011 Sep 6.
  46. Liao, X, Xue, H, Wang, YC, Nazor, KL, Guo, S, Trivedi, N, Peterson, SE, Liu, Y, Loring, JF, Laurent, LC.(2013) Matched miRNA and mRNA signatures from an hESC-based in vitro model of pancreatic differentiation reveal novel regulatory interactions. J Cell Sci. 2013 Sep 1;126(Pt 17):3848-61. doi: 10.1242/jcs.123570. Epub 2013 Jun 26.
  47. Jiang, P, Chen, C, Liu, XB, Selvaraj, V, Liu, W, Feldman, DH, Liu, Y, Pleasure, DE, Li, RA, Deng, W. (2013) Generation and characterization of spiking and non-spiking oligodendroglial progenitor cells from embryonic stem cells. Stem Cells. 2013 Aug 13. doi: 10.1002/stem.1515. [Epub ahead of print]
  48. Jones, JC, Sabatini, K, Liao, X, Tran, HT, Lynch, CL, Morey, RE, Glenn-Pratol,a V, Boscolo, FS, Yang, Q, Parast, MM, Liu, Y, Peterson, SE, Laurent, LC, Loring, JF, Wang, YC. (2013) Melanocytes derived from transgene-free human induced pluripotent stem cells. J Invest Dermatol. 2013 Aug;133(8):2104-8. doi: 10.1038/jid.2013.139. Epub 2013 Mar 20.
  49. Xue H, Wu J, Li S, Rao MS, Liu Y. (2014) Genetic modification in human pluripotent stem cells by homologous recombination and CRISPR/Cas9 System. Methods Mol Biol. 2014 Mar 11. [Epub ahead of print] PMID:24615461
  50. Jiang P, Chen C, Wang R, Chechneva OV, Chung SH, Rao MS, Pleasure DE, Liu Y, Zhang Q, Deng W (2013) hESC-derived Olig2(+) progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury. Nat Commun. 2013 Jul 23;4:2196. doi: 10.1038/ncomms3196. PMID:23880652
  51. Chen, C., Jiang, P., Xue, H., Peterson, S., Tran, H.T., McCann, A., Parast, M., Li, S., Pleasure, D.E., Laurent, L.C., Loring, J. F., Liu, Y.*, and Deng, W*. (2014) Role of astroglia in Down Syndrome revealed by patient-derived human induced pluripotent stem cells. Nat Commun. (*corresponding authors) Jul 18;5:4430. doi: 10.1038/ncomms5430
  52. Li, S., Xue, H., Long, B., Sun, L., Truong, T., and Liu, Y. (2015) Efficient generation of hiPSC neural lineage specific knockin reporters using the CRISPR/Cas9 and Cas9 double nickase system. J Vis Exp. e52539, doi:10.3791/52539.
  53. Liu, Y. Treating spinal cord injury using human iPSC derived neural progenitor populations. NRC Newsletter, Volume 20, Number 2, Spring 2015

BOOK CHAPTERS

  1. Liu, Y., and Rao, M. (2005). Transdifferentiation in the nervous system, In Neural Development and Stem Cells (New Jersey: Humana Press), pp. 249-266.
  2. Wu, Y., Liu, Y., Chesnut, J. D., and Rao, M. S. (2008). Isolation of neural stem and precursor cells from rodent tissue. Methods Mol Biol 438, 39-53.
  3. Liu, Y., Lakshmipathy, U., Ozgenc, A., Thyagarajan, B, Lieu, P., Fontes, A., Xue, H., Scheyhing, K., MacArthur, C., and Chesnut, J. D. (2010). hESC engineering by integrase-mediated chromosomal targeting. human stem cell protocols, Methods in Molecular Biology 584, pp 229-268 Turksen, K. (ed.). DOI 10.1007/978-1-60761-369-5_13, Humana Press, a part of Springer Science+Business Media, LLC
  4. Liu, Y. and Rao, M. S. (2011). Gene targeting in human pluripotent stem cells. Methods and Protocols. Schwartz, P. H, and Wesselschmidt R (eds). Humana Press, a part of Springer Science+Business Media, LLC. Methods Mol Biol. 2011;767:355-367.
  5. Han, S, McCann, A, Laurent, LC, Loring JF, and Liu, Y. (2011) Improving gene targeting efficiency in human pluripotent stem cells. in Primary and stem cells: gene transfer technologies and applications. First edition. Lakshmipathy, U & Thyagarajan, B (eds). pp211-225, John Wiley & Sons, Inc.
  6. Lieu, P,, Thyagarajan, B., Lakshmipathy, U., Chesnut, J., Liu, Y. (2012) Lentiviral vector systems for transgene delivery. In Human Stem Cell Manual , Loring, JF & Peterson, SE (eds):, Second edition pp 463-483,  Elsevier Inc.
  7. Han, S. Liu, Y. (2012) Gene targeting by homologous recombination in human pluripotent stem cells. In Human Stem Cell Manual, J.F. Loring & S.E. Peterson (eds):, Second edition. pp 485-498,  Elsevier Inc.
  8. Liu, Y. Wagner, K, and Lakshmipathy, U.(2013) Stable transfection using episomal vectors to create modified human embryonic stem cells. In Pluripotent Stem Cells: Methods and Protocols, Methods in Molecular Biology Lakshmipathy, U & Vemuri, M, C. (eds.) vol. 997, DOI 10.1007/978-1-62703-348-0_21, Springer Science+Business Media New York