3D Brain Organoids and Tumor Organoids

3D Brain Organoids and Tumor Organoids

We developed protocols to produce brain region-and sub-region-specific organoids from patient iPSC, including forebrain, midbrain, hypothalamus, arcuate nucleus, and choroid plexus. We have also significantly improved organoid technology to better mimic human embryonic cortical development. For example, we have generated forebrain organoids exhibiting human specific features, including similar cellular composition (including outer radial glia cells, cortical neurons of all six layers, human specific astrocytes and oligodendrocytes), architecture (with distinct oSVZ and upper and deeper cortical layers), molecular signatures as in the developing human brain. We have used these platforms to examine basic mechanisms regulating human brain development and associated brain disorders, such as psychiatric disorders, Zika virus and SARS-CoV2 infection. We have also developed novel protocols to generate glioblastoma tumor organoids from patient surgical samples that maintain the tumor heterogeneity and microenvironment for testing personized treatment in parallel with clinical trials.    


Selected Publications

Huang WK, Wong SZH, Pather SR, Nguyen PTT, Zhang F, Zhang DY, Zhang Z, Lu L, Fang W, Chen L, Fernandes A, Su Y, Song H, Ming GL. Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells. Cell Stem Cell. 2021 Sep 2;28(9):1657-1670.e10. doi: 10.1016/j.stem.2021.04.006. Epub 2021 May 6. PMID: 33961804; PMCID: PMC8419002.

Jacob F, Pather SR, Huang WK, Wong SZH, Zhou H, Zhang F, Cubitt B, Chen CZ, Xu M, Pradhan M, Zhang DY, Zheng W, Bang AG, Song H, de A Torre JC, Ming GL. Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism. bioRxiv [Preprint]. 2020 Jul 28:2020.07.28.225151. doi: 10.1101/2020.07.28.225151. Update in: Cell Stem Cell. 2020 Sep 21;: PMID: 32766575; PMCID: PMC7402032.

Qian X, Su Y, Adam CD, Deutschmann AU, Pather SR, Goldberg EM, Su K, Li S, Lu L, Jacob F, Nguyen PTT, Huh S, Hoke A, Swinford-Jackson SE, Wen Z, Gu X, Pierce RC, Wu H, Briand LA, Chen HI, Wolf JA, Song H, Ming GL. Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation. Cell Stem Cell. 2020 May 7;26(5):766-781.e9. doi: 10.1016/j.stem.2020.02.002. Epub 2020 Mar 5.

Jacob F, Salinas RD, Zhang DY, Nguyen PTT, Schnoll JG, Wong SZH, Thokala R, Sheikh S, Saxena D, Prokop S, Liu DA, Qian X, Petrov D, Lucas T, Chen HI, Dorsey JF, Christian KM, Binder ZA, Nasrallah M, Brem S, O'Rourke DM, Ming GL, Song H. A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. Cell. 2020 Jan 9;180(1):188-204.e22. doi: 10.1016/j.cell.2019.11.036. Epub 2019 Dec 26. 

Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, TCW J, Kouznetsova J, Ogden SC, Hammack C, Jacob F, Nguyen HN, Itkin M, Hanna C, Shinn P, Allen C, Michael SG, Simeonov A, Huang W, Christian KM, Goate A, Brennand KJ, Huang R, Xia M, Ming G-l*, Zheng W*, Song H*, Tang H*. (2016) Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nature Medicine 22, 1101-07. PMCID in progress

Zhang F, Hammack C, Ogden SC, Cheng Y, Lee EM, Wen Z, Qian X, Nguyen HN, Li Y, Yao B, Xu M, Xu T, Chen L, Wang Z, Feng H, Huang WK, Yoon KJ, Shan C, Huang L, Qin Z, Christian KM, Shi PY, Xu M, Xia M, Zheng W, Wu H, Song H*, Tang H*, Ming G-l*, Jin P*. (2016) Molecular signatures associated with ZIKV exposure in human cortical neural progenitors. Nucleic Acids Research 44, 8610-20. PMC5063002.

Tang H*, Hammack C, Ogden SC, Wen Z, Qian X, Li Y, Yao B, Shin J, Zhang F, Lee EM, Christian KM, Didier RA, Jin P, Song H*, Ming G-l.* (2016) Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell 18, 587-90. PMCID in progress.

Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, Yao B, Hamersky G, Jacob F, Zhong C, Yoon K-j, Jeang W, Lin L, Li Y, Thakor J, Berg D, Zhang C, Kang E, Chickering M, Nauen D, Ho C-Y, Wen Z, Christian KM, Shi P-Y, Maher BJ, Wu H, Jin P, Tang H, Song H*, Ming G-l*. (2016) Brain region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238-54. PMC4900885.