iPSCs & Neurological Disorders
Modeling neurological and psychiatric disorders using patient-derived iPSCs
Complementary to in vivo mouse models, we have been using patient-derived induced pluripotent stem cells (iPSCs) as a disease-in-a-dish model. We have derived iPSCs from patients with various neurological disorders, including autism spectrum disorders (with MECP2 mutations or 15q11.2 duplications) and schizophrenia (with mutations in DISC1 or Neurexin, or 15q11.2 deletions). Using modern gene editing approaches, we aim to understand how genetic risk factors contribute to cellular phenotypes and disease pathology. We are also interested in developing drug screening platforms based on these cellular phenotypes.
Selected Publications
Kim NS, Ringeling FR, Zhou Y, Nguyen HN, Temme SJ, Lin YT, Eacker S, Dawson VL, Dawson TM, Xiao B, Hsu KS, Canzar S, Li W, Worley P, Christian KM, Yoon KJ, Song H, Ming GL. CYFIP1 Dosages Exhibit Divergent Behavioral Impact via Diametric Regulation of NMDA Receptor Complex Translation in Mouse Models of Psychiatric Disorders. Biol Psychiatry. 2022 Nov 15;92(10):815-826. doi: 10.1016/j.biopsych.2021.04.023. Epub 2021 May 5.
Kim NS, Wen Z, Liu J, Zhou Y, Guo Z, Xu C, Lin YT, Yoon KJ, Park J, Cho M, Kim M, Wang X, Yu H, Sakamuru S, Christian KM, Hsu KS, Xia M, Li W, Ross CA, Margolis RL, Lu XY, Song H, Ming GL. Pharmacological rescue in patient iPSC and mouse models with a rare DISC1 mutation. Nat Commun. 2021 Mar 3;12(1):1398. doi: 10.1038/s41467-021-21713-3. Erratum in: Nat Commun. 2021 Apr 30;12(1):2570.
Wen Z, Christian KM, Song H, Ming GL. Modeling psychiatric disorders with patient-derived iPSCs. Current opinion in neurobiology. 2016; 36:118-27. NIHMSID: NIHMS745480 PubMed [journal] PMID: 26705693, PMCID: PMC4738077
Wen Z, Nguyen HN, Guo Z, Lalli MA, Wang X, Su Y, Kim NS, Yoon KJ, Shin J, Zhang C, Makri G, Nauen D, Yu H, Guzman E, Chiang CH, Yoritomo N, Kaibuchi K, Zou J, Christian KM, Cheng L, Ross CA, Margolis RL, Chen G, Kosik KS, Song H, Ming, G-l. (2014). Synaptic dysregulation in a human iPS cell model of mental disorders. Nature 515, 414-8. [PMC4501856]
Yoon, K.J., Nguyen, H.N., Ursini, G., Zhang, F., Kim, N-S., Wen, Z., Makri, G., Nauen, D., Shin, J.H., Park, Y., Chung, R., Pekle, E., Zhang, C., Towe, M., Hussaini S, M.Q., Lee, Y., Rujescu, D., St. Clair, D., Kleinman, J.E., Hyde, T.M., Krauss, G., Christian, K.M., Rapoport, J.L., Weinberger, D.R., Song, H-j., and Ming, G-l. (2014). Modelling a risk factor for schizophrenia in iPSCs and mice reveals neural stem cell function associated with adherens junctions and polarity. Cell Stem Cell 15, 79-91. [PMC4237009]
The Huntington’s Disease iPSC Consortium. (2012). Induced pluripotent stem cells from patients with Huntington’s disease show CAG repeat expansion associated phenotypes. Cell Stem Cell 11, 264-78. [PMC3804072]
Chiang CH, Su Y, Wen Z, Yoritomo N, Ross CA, Margolis RL, Song H, Ming GL. Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Molecular psychiatry. 2011; 16(4):358-60. NIHMSID: NIHMS545745 PubMed [journal] PMID: 21339753, PMCID: PMC4005725