![Meng Li](https://profiles-cardiff.imgix.net/attachments/1103?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Professor Meng Li
Chair in Stem Cell Neurobiology, Neuroscience and Mental Health Innovation Institute
- LiM26@cardiff.ac.uk
- +44 29206 88345
- Hadyn Ellis Building, Room Room 3.39, Maindy Road, Cardiff, CF24 4HQ
Overview
Research overview
Meng Li's group is interested in elucidating the molecular mechanisms underlining neural fate specification and the subsequent differentiation of neuroectoderm cells into defined neuronal subtypes.
We aim to exploit iPSC-derived neurons for elucidating the cellular basis of neuropsychiatric diseases and developing better strategies for cell therapies.
We employ an integrated experimental approach involving in vitro neural development of human and mouse embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), as well as contemporary genetic manipulation in model organisms.
We apply the resulting knowledge to devise novel strategies that drive pluripotent stem cells into clinically important neurons, such as midbrain dopamine neuron, striatal GABAergic neurons and cortical interneurons.
Publication
2024
- Cabezas De La Fuente, D. et al. 2024. Impaired oxysterol-liver X receptor signaling underlies aberrant cortical neurogenesis in a human stem cell model of neurodevelopmental disorder. Cell Reports 43(3), article number: 113946. (10.1016/j.celrep.2024.113946)
- Hennegan, J. et al. 2024. Inhibition of 7α,26-dihydroxycholesterol biosynthesis promotes midbrain dopaminergic neuron development. iScience 27(1), article number: 108670. (10.1016/j.isci.2023.108670)
- Li, Z. et al. 2024. Differential growth and transcriptomic profile of stem cell-derived midbrain astrocytes. eLife
2023
- Fernandez Cardo, L., Monzón Sandoval, J., Li, Z., Webber, C. and Li, M. 2023. Single-cell transcriptomics and In vitro lineage tracing reveals differential susceptibility of human iPSC-derived midbrain dopaminergic neurons in a cellular model of Parkinson's Disease. Cells 12(24), article number: 2860. (10.3390/cells12242860)
- Fjodorova, M., Noakes, Z., Cabezas De La Fuente, D., Errington, A. and Li, M. 2023. Dysfunction of cAMP-Protein Kinase A-calcium signaling axis in striatal medium spiny neurons: a role in schizophrenia and Huntington’s disease neuropathology. Biological Psychiatry: Global Open Science 3(3), pp. 418-429. (10.1016/j.bpsgos.2022.03.010)
- Keefe, F., Monzon Sandoval, J., Rosser, A. E., Webber, C. and Li, M. 2023. Single-cell transcriptomics reveals conserved regulatory networks in human and mouse interneuron development. International Journal of Molecular Sciences 24(9), article number: 8122. (10.3390/ijms24098122)
- Sperandeo, A. et al. 2023. Cortical neuronal hyperexcitability and synaptic changes in SGCE mutation-positive myoclonus dystonia. Brain 146(4), pp. 1523-1541. (10.1093/brain/awac365)
- Fernandez Cardo, L., de la Fuente, D. C. and Li, M. 2023. Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder. Molecular Autism 14, article number: 8. (10.1186/s13229-023-00540-x)
- Cameron, D. et al. 2023. Single nuclei RNA sequencing of 5 regions of the human prenatal brain implicates developing neuron populations in genetic risk for schizophrenia. Biological Psychiatry 93, pp. 157-166. (10.1016/j.biopsych.2022.06.033)
2022
- Cruz Santos, M., Fernandez Cardo, L. and Li, M. 2022. A novel LHX6 reporter cell line for tracking human iPSC-derived cortical interneurons. Cells 11(5), article number: 853. (10.3390/cells11050853)
2021
- Cruz Santos, M. and Li, M. 2021. Identification of TGFβ signalling as a regulator of interneuron neurogenesis in a human pluripotent stem cell model. Neuronal Signaling 5(4), article number: NS20210020. (10.1042/NS20210020)
- Badin, R. A. et al. 2021. Stem cells for Huntington’s disease (SC4HD): an international consortium to facilitate stem cell-based therapy for Huntington’s disease. Journal of Huntington's Disease 10(2), pp. 221-226. (10.3233/JHD-210473)
2020
- Li, M., Noakes, Z. and Fjodorova, M. 2020. A role for TGFβ signalling in medium spiny neuron differentiation of human pluripotent stem cells. Neuronal Signaling 4(2), article number: NS20200004. (10.1042/NS20200004)
- Precious, S. V. et al. 2020. Dopaminergic progenitors derived from epiblast stem cells function similarly to primary VM-derived progenitors when transplanted into a Parkinson’s disease model. Frontiers in Neuroscience 14, article number: 312. (10.3389/fnins.2020.00312)
2019
- Li, M. and Keefe, F. 2019. Pluripotent stem cell derived inhibitory interneurons - principles and applications in health and disease. Neural Regeneration Research 15(2), pp. 251-252. (10.4103/1673-5374.265547)
- Fjodorova, M. et al. 2019. CTIP2-regulated reduction in PKA-dependent DARPP32 phosphorylation in human medium spiny neurons: implications for Huntington’s disease. Stem Cell Reports 13(3-6), pp. 448-457. (10.1016/j.stemcr.2019.07.015)
- Noakes, Z. et al. 2019. Human pluripotent stem cell-derived striatal interneurons: differentiation and maturation in vitro and in the rat brain. Stem Cell Reports 12(2), pp. 191-200. (10.1016/j.stemcr.2018.12.014)
2018
- Lai, B. et al. 2018. A modular assembly of spinal cord-like tissue allows targeted tissue repair in the transected spinal cord. Advanced Science 5(9), article number: 1800261. (10.1002/advs.201800261)
- Merkouris, S. et al. 2018. Fully human agonist antibodies to TrkB using autocrine cell-based selection from a combinatorial antibody library. Proceedings of the National Academy of Sciences 115(30), pp. E7023-E7032. (10.1073/pnas.1806660115)
- Fjodorova, M. and Li, M. 2018. Robust induction of DARPP32-expressing GABAergic striatal neurons from human pluripotent stem cells. In: Precious, S., Rosser, A. and Dunnett, S. eds. Huntington’s Disease., Vol. 1780. Methods in Molecular Biology New York: Humana Press, pp. 585-605., (10.1007/978-1-4939-7825-0_27)
- De Gregorio, R. et al. 2018. miR-34b/c regulates Wnt1 and enhances mesencephalic dopaminergic neuron differentiation. Stem Cell Reports 10(4), pp. 1237-1250. (10.1016/j.stemcr.2018.02.006)
- De Clercq, S. et al. 2018. DMRT5 together with DMRT3 directly controls hippocampus development and neocortical area map formation. Cerebral Cortex 28(2), pp. 493-509. (10.1093/cercor/bhw384)
2017
- Ferrai, C. et al. 2017. RNA polymerase II primes Polycomb-repressed developmental genes throughout terminal neuronal differentiation. Molecular Systems Biology 13(10), article number: 946. (10.15252/msb.20177754)
- Young, F. I., Keruzore, M., Nan, X., Gennet, N., Bellefroid, E. J. and Li, M. 2017. The Doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1. Proceedings of the National Academy of Sciences 114(28), pp. E5599-E5607. (10.1073/pnas.1705186114)
- Tamburini, C. and Li, M. 2017. Understanding neurodevelopmental disorders using human pluripotent stem cell-derived neurons. Brain Pathology 27(4), pp. 508-517. (10.1111/bpa.12517)
- Li, M. and Rosser, A. E. 2017. Pluripotent stem cell-derived neurons for transplantation in Huntington's disease. In: Howard, C. J. ed. Functional Neural Transplantation. Progress in Brain Research Elsevier, pp. 263-281., (10.1016/bs.pbr.2017.02.009)
2016
- Gennet, N., Tamburini, C., Nan, X. and Li, M. 2016. FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons. Scientific Reports 6, article number: 32488. (10.1038/srep32488)
- Noakes, Z., Fjodorova, M. and Li, M. 2016. Deriving striatal projection neurons from human pluripotent stem cells with activin A. Neural Regeneration Research 10(12), pp. 1914-1916. (10.4103/1673-5374.169621)
2015
- Fjodorova, M., Noakes, Z. and Li, M. 2015. How to make striatal projection neurons. Neurogenesis 2(1), article number: e1100227. (10.1080/23262133.2015.1100227)
- Arber, C. et al. 2015. Activin A directs striatal projection neuron differentiation of human pluripotent stem cells. Development 142(7), pp. 1375-1386. (10.1242/dev.117093)
2014
- Craddock, N. J. et al. 2014. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations. Schizophrenia Bulletin 40(4), pp. 729-736. (10.1093/schbul/sbu069)
2013
- Chang, K. and Li, M. 2013. Clonal isolation of an intermediate pluripotent stem cell state. Stem Cells 31(5), pp. 918-927. (10.1002/stem.1330)
- Arber, C. and Li, M. 2013. Cortical interneurons from human pluripotent stem cells: prospects for neurological and psychiatric disease. Frontiers in Cellular Neuroscience 7, article number: 10. (10.3389/fncel.2013.00010)
2012
- Cambray, S. et al. 2012. Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors. Nature Communications 3, article number: 841. (10.1038/ncomms1817)
- Smith, G. A. et al. 2012. L-dopa and graft-induced dyskinesia in the 6-OHDA-lesioned mouse [Abstract]. Cell Transplantation 21(4), pp. 792-792.
- Shin, E., Palmer, M. J., Li, M. and Fricker, R. A. 2012. GABAergic neurons from mouse embryonic stem cells possess functional properties of striatal neurons in vitro, and develop into striatal neurons in vivo in a mouse model of huntington's disease. Stem Cell Reviews 8(2), pp. 513-531. (10.1007/s12015-011-9290-2)
2011
- Jaeger, I. et al. 2011. Temporally controlled modulation of FGF/ERK signaling directs midbrain dopaminergic neural progenitor fate in mouse and human pluripotent stem cells. Development 138(20), pp. 4363-4374. (10.1242/dev.066746)
- Gennet, N. et al. 2011. Doublesex and mab-3-related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate. Proceedings of the National Academy of Sciences 108(22), pp. 9131-9136. (10.1073/pnas.1016679108)
- Surmacz, B., Noisa, P., Risner-Janiczek, J. R., Hui, K., Ungless, M., Cui, W. and Li, M. 2011. DLK1 promotes neurogenesis of human and mouse pluripotent stem cell-derived neural progenitors via modulating notch and BMP signalling. Stem Cell Reviews 8(2), pp. 459-471. (10.1007/s12015-011-9298-7)
- Peng, C., Aron, L., Klein, R., Li, M., Wurst, W., Prakash, N. and Le, W. 2011. Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons. Journal of Neuroscience 31(36), pp. 12802-12815. (10.1523/JNEUROSCI.0898-11.2011)
- Risner-Janiczek, J. R., Ungless, M. A. and Li, M. 2011. Electrophysiological properties of embryonic stem cell-derived neurons. PLoS ONE 6(8), article number: e24169. (10.1371/journal.pone.0024169)
- Farley, E. K., Gale, E., Chambers, D. and Li, M. 2011. Effects of in ovo electroporation on endogenous gene expression: genome-wide analysis. Neural Development 6(1), article number: 17. (10.1186/1749-8104-6-17)
2010
- Konstantoulas, C. J., Parmar, M. and Li, M. 2010. FoxP1 promotes midbrain identity in embryonic stem cell-derived dopamine neurons by regulating Pitx3. Journal of Neurochemistry 113(4), pp. 836-847. (10.1111/j.1471-4159.2010.06650.x)
- Noisa, P., Urrutikoetxea-Uriguen, A., Li, M. and Cui, W. 2010. Generation of human embryonic stem cell reporter lines expressing GFP specifically in neural progenitors. Stem Cell Reviews 6(3), pp. 438-449. (10.1007/s12015-010-9159-9)
- Grealish, S., Jonsson, M. E., Li, M., Kirik, D., Bjorklund, A. and Thompson, L. H. 2010. The A9 dopamine neuron component in grafts of ventral mesencephalon is an important determinant for recovery of motor function in a rat model of Parkinson's disease. Brain 133(2), pp. 482-495. (10.1093/brain/awp328)
- Uhde, C. W., Vives, J., Jaeger, I. and Li, M. 2010. Rmst Is a novel marker for the mouse ventral mesencephalic floor plate and the anterior dorsal midline cells. PLoS ONE 5(1), article number: e8641. (10.1371/journal.pone.0008641)
2009
- Tsakiridis, A. et al. 2009. Microsphere-based tracing and molecular delivery in embryonic stem cells. Biomaterials 30(29), pp. 5853-5861. (10.1016/j.biomaterials.2009.06.024)
- Ho, H., Chang, K., Nichols, J. and Li, M. 2009. Homeodomain protein Pitx3 maintains the mitotic activity of lens epithelial cells. Mechanisms of Development 126(1-2), pp. 18-29. (10.1016/j.mod.2008.10.007)
- Gennet, N. et al. 2009. Microspheres as a vehicle for biomolecule delivery to neural stem cells. New Biotechnology 25(6), pp. 442-449. (10.1016/j.nbt.2009.05.006)
2008
- Vives, J., Sasajala, P., Chang, K. H., Zhao, S. and Li, M. 2008. A mouse model for tracking nigrostriatal dopamine neuron axon growth. genesis 46(3), pp. 125-131. (10.1002/dvg.20375)
- Nordin, N., Li, M. and Mason, J. O. 2008. Expression profiles of Wnt genes during neural differentiation of mouse embryonic stem cells. Cloning and Stem Cells 10(1), pp. 37-48. (10.1089/clo.2007.0060)
- Nordin, N., Nathan, S., Li, M. and Mason, J. O. 2008. Inducible transgene expression in undifferentiated mouse embryonic stem cells and embryoid bodies. The Medical Journal of Malaysia 63(Supp A), pp. 59-60.
2007
- Labouèbe, G. et al. 2007. RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nature Neuroscience 10(12), pp. 1559-1568. (10.1038/nn2006)
- Parmar, M. and Li, M. 2007. Early specification of dopaminergic phenotype during ES cell differentiation. BMC Developmental Biology 7, article number: 86. (10.1186/1471-213X-7-86)
2006
- Sottile, V., Li, M. and Scotting, P. J. 2006. Stem cell marker expression in the Bergmann glia population of the adult mouse brain. Brain Research 1099(1), pp. 8-17. (10.1016/j.brainres.2006.04.127)
- Ho, H. and Li, M. 2006. Potential application of embryonic stem cells in Parkinson's disease: drug screening and cell therapy [Review]. Regenerative Medicine 1(2), pp. 175-182. (10.2217/17460751.1.2.175)
2005
- Maxwell, S. L. and Li, M. 2005. Midbrain dopaminergic development in vivo and in vitro from embryonic stem cells. Journal of Anatomy 207(3), pp. 209-218. (10.1111/j.1469-7580.2005.00453.x)
- Maxwell, S. L., Ho, H., Kuehner, E., Zhao, S. and Li, M. 2005. Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development. Developmental Biology 282(2), pp. 467-479. (10.1016/j.ydbio.2005.03.028)
2004
- Zhao, S., Nichols, J., Smith, A. G. and Li, M. 2004. SoxB transcription factors specify neuroectodermal lineage choice in ES cells. Molecular and Cellular Neuroscience 27(3), pp. 332-342. (10.1016/j.mcn.2004.08.002)
- Zhao, S. et al. 2004. Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neurons. European Journal of Neuroscience 19(5), pp. 1133-1140. (10.1111/j.1460-9568.2004.03206.x)
2003
- Aubert, J. et al. 2003. Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knock-in mice. Proceedings of the National Academy of Sciences of the United States of America 100(Supp 1), pp. 11836-11841. (10.1073/pnas.1734197100)
2002
- Lauer, P., Metzner, H. J., Zettlmeissl, G., Li, M., Smith, A. G., Lathe, R. and Dickneite, G. 2002. Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit. Thrombosis and Haemostasis 88(6), pp. 967-974.
- Li, M. 2002. Lineage selection for generation and amplification of neural precursor cells. In: Turksen, K. ed. Embryonic Sten Cells: Methods and Protocols. Methods in Molecular Biology Vol. 185. Totowa, NJ: Humana Press, pp. 202-215., (10.1385/1-59259-241-4:205)
2001
- Li, M., Price, D. and Smith, A. 2001. Lineage selection and isolation of neural precursors from embryonic stem cells. Symposia of the Society for Experimental Biology 53, pp. 29-42.
1999
- Aubert, J. et al. 1999. Leukemia inhibitory factor and its receptor promote adipocyte differentiation via the Mitogen-activated protein kinase cascade. Journal of Biological Chemistry 274(35), pp. 24965-24972. (10.1074/jbc.274.35.24965)
Articles
- Cabezas De La Fuente, D. et al. 2024. Impaired oxysterol-liver X receptor signaling underlies aberrant cortical neurogenesis in a human stem cell model of neurodevelopmental disorder. Cell Reports 43(3), article number: 113946. (10.1016/j.celrep.2024.113946)
- Hennegan, J. et al. 2024. Inhibition of 7α,26-dihydroxycholesterol biosynthesis promotes midbrain dopaminergic neuron development. iScience 27(1), article number: 108670. (10.1016/j.isci.2023.108670)
- Li, Z. et al. 2024. Differential growth and transcriptomic profile of stem cell-derived midbrain astrocytes. eLife
- Fernandez Cardo, L., Monzón Sandoval, J., Li, Z., Webber, C. and Li, M. 2023. Single-cell transcriptomics and In vitro lineage tracing reveals differential susceptibility of human iPSC-derived midbrain dopaminergic neurons in a cellular model of Parkinson's Disease. Cells 12(24), article number: 2860. (10.3390/cells12242860)
- Fjodorova, M., Noakes, Z., Cabezas De La Fuente, D., Errington, A. and Li, M. 2023. Dysfunction of cAMP-Protein Kinase A-calcium signaling axis in striatal medium spiny neurons: a role in schizophrenia and Huntington’s disease neuropathology. Biological Psychiatry: Global Open Science 3(3), pp. 418-429. (10.1016/j.bpsgos.2022.03.010)
- Keefe, F., Monzon Sandoval, J., Rosser, A. E., Webber, C. and Li, M. 2023. Single-cell transcriptomics reveals conserved regulatory networks in human and mouse interneuron development. International Journal of Molecular Sciences 24(9), article number: 8122. (10.3390/ijms24098122)
- Sperandeo, A. et al. 2023. Cortical neuronal hyperexcitability and synaptic changes in SGCE mutation-positive myoclonus dystonia. Brain 146(4), pp. 1523-1541. (10.1093/brain/awac365)
- Fernandez Cardo, L., de la Fuente, D. C. and Li, M. 2023. Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder. Molecular Autism 14, article number: 8. (10.1186/s13229-023-00540-x)
- Cameron, D. et al. 2023. Single nuclei RNA sequencing of 5 regions of the human prenatal brain implicates developing neuron populations in genetic risk for schizophrenia. Biological Psychiatry 93, pp. 157-166. (10.1016/j.biopsych.2022.06.033)
- Cruz Santos, M., Fernandez Cardo, L. and Li, M. 2022. A novel LHX6 reporter cell line for tracking human iPSC-derived cortical interneurons. Cells 11(5), article number: 853. (10.3390/cells11050853)
- Cruz Santos, M. and Li, M. 2021. Identification of TGFβ signalling as a regulator of interneuron neurogenesis in a human pluripotent stem cell model. Neuronal Signaling 5(4), article number: NS20210020. (10.1042/NS20210020)
- Badin, R. A. et al. 2021. Stem cells for Huntington’s disease (SC4HD): an international consortium to facilitate stem cell-based therapy for Huntington’s disease. Journal of Huntington's Disease 10(2), pp. 221-226. (10.3233/JHD-210473)
- Li, M., Noakes, Z. and Fjodorova, M. 2020. A role for TGFβ signalling in medium spiny neuron differentiation of human pluripotent stem cells. Neuronal Signaling 4(2), article number: NS20200004. (10.1042/NS20200004)
- Precious, S. V. et al. 2020. Dopaminergic progenitors derived from epiblast stem cells function similarly to primary VM-derived progenitors when transplanted into a Parkinson’s disease model. Frontiers in Neuroscience 14, article number: 312. (10.3389/fnins.2020.00312)
- Li, M. and Keefe, F. 2019. Pluripotent stem cell derived inhibitory interneurons - principles and applications in health and disease. Neural Regeneration Research 15(2), pp. 251-252. (10.4103/1673-5374.265547)
- Fjodorova, M. et al. 2019. CTIP2-regulated reduction in PKA-dependent DARPP32 phosphorylation in human medium spiny neurons: implications for Huntington’s disease. Stem Cell Reports 13(3-6), pp. 448-457. (10.1016/j.stemcr.2019.07.015)
- Noakes, Z. et al. 2019. Human pluripotent stem cell-derived striatal interneurons: differentiation and maturation in vitro and in the rat brain. Stem Cell Reports 12(2), pp. 191-200. (10.1016/j.stemcr.2018.12.014)
- Lai, B. et al. 2018. A modular assembly of spinal cord-like tissue allows targeted tissue repair in the transected spinal cord. Advanced Science 5(9), article number: 1800261. (10.1002/advs.201800261)
- Merkouris, S. et al. 2018. Fully human agonist antibodies to TrkB using autocrine cell-based selection from a combinatorial antibody library. Proceedings of the National Academy of Sciences 115(30), pp. E7023-E7032. (10.1073/pnas.1806660115)
- De Gregorio, R. et al. 2018. miR-34b/c regulates Wnt1 and enhances mesencephalic dopaminergic neuron differentiation. Stem Cell Reports 10(4), pp. 1237-1250. (10.1016/j.stemcr.2018.02.006)
- De Clercq, S. et al. 2018. DMRT5 together with DMRT3 directly controls hippocampus development and neocortical area map formation. Cerebral Cortex 28(2), pp. 493-509. (10.1093/cercor/bhw384)
- Ferrai, C. et al. 2017. RNA polymerase II primes Polycomb-repressed developmental genes throughout terminal neuronal differentiation. Molecular Systems Biology 13(10), article number: 946. (10.15252/msb.20177754)
- Young, F. I., Keruzore, M., Nan, X., Gennet, N., Bellefroid, E. J. and Li, M. 2017. The Doublesex-related Dmrta2 safeguards neural progenitor maintenance involving transcriptional regulation of Hes1. Proceedings of the National Academy of Sciences 114(28), pp. E5599-E5607. (10.1073/pnas.1705186114)
- Tamburini, C. and Li, M. 2017. Understanding neurodevelopmental disorders using human pluripotent stem cell-derived neurons. Brain Pathology 27(4), pp. 508-517. (10.1111/bpa.12517)
- Gennet, N., Tamburini, C., Nan, X. and Li, M. 2016. FolR1: a novel cell surface marker for isolating midbrain dopamine neural progenitors and nascent dopamine neurons. Scientific Reports 6, article number: 32488. (10.1038/srep32488)
- Noakes, Z., Fjodorova, M. and Li, M. 2016. Deriving striatal projection neurons from human pluripotent stem cells with activin A. Neural Regeneration Research 10(12), pp. 1914-1916. (10.4103/1673-5374.169621)
- Fjodorova, M., Noakes, Z. and Li, M. 2015. How to make striatal projection neurons. Neurogenesis 2(1), article number: e1100227. (10.1080/23262133.2015.1100227)
- Arber, C. et al. 2015. Activin A directs striatal projection neuron differentiation of human pluripotent stem cells. Development 142(7), pp. 1375-1386. (10.1242/dev.117093)
- Craddock, N. J. et al. 2014. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations. Schizophrenia Bulletin 40(4), pp. 729-736. (10.1093/schbul/sbu069)
- Chang, K. and Li, M. 2013. Clonal isolation of an intermediate pluripotent stem cell state. Stem Cells 31(5), pp. 918-927. (10.1002/stem.1330)
- Arber, C. and Li, M. 2013. Cortical interneurons from human pluripotent stem cells: prospects for neurological and psychiatric disease. Frontiers in Cellular Neuroscience 7, article number: 10. (10.3389/fncel.2013.00010)
- Cambray, S. et al. 2012. Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors. Nature Communications 3, article number: 841. (10.1038/ncomms1817)
- Smith, G. A. et al. 2012. L-dopa and graft-induced dyskinesia in the 6-OHDA-lesioned mouse [Abstract]. Cell Transplantation 21(4), pp. 792-792.
- Shin, E., Palmer, M. J., Li, M. and Fricker, R. A. 2012. GABAergic neurons from mouse embryonic stem cells possess functional properties of striatal neurons in vitro, and develop into striatal neurons in vivo in a mouse model of huntington's disease. Stem Cell Reviews 8(2), pp. 513-531. (10.1007/s12015-011-9290-2)
- Jaeger, I. et al. 2011. Temporally controlled modulation of FGF/ERK signaling directs midbrain dopaminergic neural progenitor fate in mouse and human pluripotent stem cells. Development 138(20), pp. 4363-4374. (10.1242/dev.066746)
- Gennet, N. et al. 2011. Doublesex and mab-3-related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate. Proceedings of the National Academy of Sciences 108(22), pp. 9131-9136. (10.1073/pnas.1016679108)
- Surmacz, B., Noisa, P., Risner-Janiczek, J. R., Hui, K., Ungless, M., Cui, W. and Li, M. 2011. DLK1 promotes neurogenesis of human and mouse pluripotent stem cell-derived neural progenitors via modulating notch and BMP signalling. Stem Cell Reviews 8(2), pp. 459-471. (10.1007/s12015-011-9298-7)
- Peng, C., Aron, L., Klein, R., Li, M., Wurst, W., Prakash, N. and Le, W. 2011. Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons. Journal of Neuroscience 31(36), pp. 12802-12815. (10.1523/JNEUROSCI.0898-11.2011)
- Risner-Janiczek, J. R., Ungless, M. A. and Li, M. 2011. Electrophysiological properties of embryonic stem cell-derived neurons. PLoS ONE 6(8), article number: e24169. (10.1371/journal.pone.0024169)
- Farley, E. K., Gale, E., Chambers, D. and Li, M. 2011. Effects of in ovo electroporation on endogenous gene expression: genome-wide analysis. Neural Development 6(1), article number: 17. (10.1186/1749-8104-6-17)
- Konstantoulas, C. J., Parmar, M. and Li, M. 2010. FoxP1 promotes midbrain identity in embryonic stem cell-derived dopamine neurons by regulating Pitx3. Journal of Neurochemistry 113(4), pp. 836-847. (10.1111/j.1471-4159.2010.06650.x)
- Noisa, P., Urrutikoetxea-Uriguen, A., Li, M. and Cui, W. 2010. Generation of human embryonic stem cell reporter lines expressing GFP specifically in neural progenitors. Stem Cell Reviews 6(3), pp. 438-449. (10.1007/s12015-010-9159-9)
- Grealish, S., Jonsson, M. E., Li, M., Kirik, D., Bjorklund, A. and Thompson, L. H. 2010. The A9 dopamine neuron component in grafts of ventral mesencephalon is an important determinant for recovery of motor function in a rat model of Parkinson's disease. Brain 133(2), pp. 482-495. (10.1093/brain/awp328)
- Uhde, C. W., Vives, J., Jaeger, I. and Li, M. 2010. Rmst Is a novel marker for the mouse ventral mesencephalic floor plate and the anterior dorsal midline cells. PLoS ONE 5(1), article number: e8641. (10.1371/journal.pone.0008641)
- Tsakiridis, A. et al. 2009. Microsphere-based tracing and molecular delivery in embryonic stem cells. Biomaterials 30(29), pp. 5853-5861. (10.1016/j.biomaterials.2009.06.024)
- Ho, H., Chang, K., Nichols, J. and Li, M. 2009. Homeodomain protein Pitx3 maintains the mitotic activity of lens epithelial cells. Mechanisms of Development 126(1-2), pp. 18-29. (10.1016/j.mod.2008.10.007)
- Gennet, N. et al. 2009. Microspheres as a vehicle for biomolecule delivery to neural stem cells. New Biotechnology 25(6), pp. 442-449. (10.1016/j.nbt.2009.05.006)
- Vives, J., Sasajala, P., Chang, K. H., Zhao, S. and Li, M. 2008. A mouse model for tracking nigrostriatal dopamine neuron axon growth. genesis 46(3), pp. 125-131. (10.1002/dvg.20375)
- Nordin, N., Li, M. and Mason, J. O. 2008. Expression profiles of Wnt genes during neural differentiation of mouse embryonic stem cells. Cloning and Stem Cells 10(1), pp. 37-48. (10.1089/clo.2007.0060)
- Nordin, N., Nathan, S., Li, M. and Mason, J. O. 2008. Inducible transgene expression in undifferentiated mouse embryonic stem cells and embryoid bodies. The Medical Journal of Malaysia 63(Supp A), pp. 59-60.
- Labouèbe, G. et al. 2007. RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nature Neuroscience 10(12), pp. 1559-1568. (10.1038/nn2006)
- Parmar, M. and Li, M. 2007. Early specification of dopaminergic phenotype during ES cell differentiation. BMC Developmental Biology 7, article number: 86. (10.1186/1471-213X-7-86)
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- Ho, H. and Li, M. 2006. Potential application of embryonic stem cells in Parkinson's disease: drug screening and cell therapy [Review]. Regenerative Medicine 1(2), pp. 175-182. (10.2217/17460751.1.2.175)
- Maxwell, S. L. and Li, M. 2005. Midbrain dopaminergic development in vivo and in vitro from embryonic stem cells. Journal of Anatomy 207(3), pp. 209-218. (10.1111/j.1469-7580.2005.00453.x)
- Maxwell, S. L., Ho, H., Kuehner, E., Zhao, S. and Li, M. 2005. Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development. Developmental Biology 282(2), pp. 467-479. (10.1016/j.ydbio.2005.03.028)
- Zhao, S., Nichols, J., Smith, A. G. and Li, M. 2004. SoxB transcription factors specify neuroectodermal lineage choice in ES cells. Molecular and Cellular Neuroscience 27(3), pp. 332-342. (10.1016/j.mcn.2004.08.002)
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- Lauer, P., Metzner, H. J., Zettlmeissl, G., Li, M., Smith, A. G., Lathe, R. and Dickneite, G. 2002. Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit. Thrombosis and Haemostasis 88(6), pp. 967-974.
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Book sections
- Fjodorova, M. and Li, M. 2018. Robust induction of DARPP32-expressing GABAergic striatal neurons from human pluripotent stem cells. In: Precious, S., Rosser, A. and Dunnett, S. eds. Huntington’s Disease., Vol. 1780. Methods in Molecular Biology New York: Humana Press, pp. 585-605., (10.1007/978-1-4939-7825-0_27)
- Li, M. and Rosser, A. E. 2017. Pluripotent stem cell-derived neurons for transplantation in Huntington's disease. In: Howard, C. J. ed. Functional Neural Transplantation. Progress in Brain Research Elsevier, pp. 263-281., (10.1016/bs.pbr.2017.02.009)
- Li, M. 2002. Lineage selection for generation and amplification of neural precursor cells. In: Turksen, K. ed. Embryonic Sten Cells: Methods and Protocols. Methods in Molecular Biology Vol. 185. Totowa, NJ: Humana Press, pp. 202-215., (10.1385/1-59259-241-4:205)
Research
The primary research interest of our laboratory is to uncover the molecular mechanisms underlying neuronal subtype specification of pluripotent stem cells and during mammalian development. Our research over the years has contributed to the advance in understanding pluripotent stem cell (PSC) neural fate conversion and dopaminergic fate specification of PSCs and during normal mammalian development. These studies led to the establishment of valuable 'tool boxes' for lineage-specific marking of defined stem/progenitors and mature dopamine neurons, and efficient novel methods for directed neuronal differentiation. Recently, we have extended our interest into GABAergic cortical interneurons, a complex group of cells which dysfunction has been implicated in neuropsychiatric diseases and epilepsy.
Molecular mechanisms controlling neurogenesis and neuronal subtype specification
Our ability to control the differentiation fate choice of pluripotent stem cells is pivotal for realising their potential in disease modelling, drug screening and cell therapy. We have recently identified the Doublesex and mab-3-related transcription factor 5 (Dmrt5) as a key factor controlling ventral midbrain neural progenitor identity and dopamine neuron differentiation. Emerging evidence also indicated the involvement of Dmrt5 function in cortical neurogenesis. Using state-of-the-art molecular and cellular tools and genetically engineered animal models, we aim to gain in depth understanding the role of Dmrt5 in forebrain and midbrain development and the underlying molecular cascade.
Model neuropsychiatric diseases with patient iPSCs
Recent genomic studies have identified a number of genetic risk factors conferring susceptibility across a spectrum of clinical phenotypes including schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), and intellectual disability. However, how the genetic variances cause dysfunction of the mind remain largely unknown. Our group has developed protocols to generate midbrain dopamine neurons and cortical interneurons, respectively, from hESCs and hiPSCs. These are two of the three major neurotransmitter phenotypes affected in psychiatric patients. We are developing cellular model to study the effects of genetic variants in neuronal development and pathophysiology using hiPSCs derived from patients with neuropsychiatric diseases.
Cell based therapy for neurodegenerative disorders
Neural transplantation remains a promising therapy to treat neurodegenerative diseases such as Parkinson's and Huntington's disease. These are characterised by preferential loss of dopamine neurons in the substantia nigra and GABAergic projection neurons in the striatum. Another objective of our group is to generate transplantable nigral and striatal progenitors from human pluripotent stem cells using culture media compatibles with clinical applications. In addition, we are using these culture systems as in vitro model of development to study the molecular mechanisms controlling neuronal specification during early mammalian development.
Grant support
- European Commission (FP7)
- The Wellcome Trust
- Medical Research Council
Group members
- Lucia Cardo
- Marija Fjodorova
- Craig Joyce
- Zoe Noakes
- John Pflug
- Krishanthi Sinnadurai
- Claudia Tamburini
- Matthieu Trigano
- Fraser Young
