Human Brain Organoid: A Versatile Tool for Modeling Neurodegeneration Diseases and for Drug Screening

Figure 1

The AD, PD, and ASD isogenic organoids derived from the patient iPSCs where their mutated genes were corrected via CRISPR-CAS9 based genome editing as well as from the iPSCs where their mutated genes were uncorrected. These isogenic organoids could recapitulate the key pathophysiological features. A-B) iPSCs and the organoids from FAD patients. a) Gene mutation was corrected via CRISPR-CAS9 based genome editing in the iPSCs derived from FAD patients and the organoids from the FAD iPSCs; b) Both iPSCs and the organoids are identical except for the uncorrected gene mutation. C-E) iPSCs and organoids from PD patients. c) mid-brain-like organoids (MOs) generated with the addition of SMADi, CHIR99021 at 3uM, and IWP2 in the culture medium; d) Gene mutation was corrected via CRISPR-CAS9 based genome editing in the iPSCs derived from PD patient and the organoids from the PD iPSCs; e) Both iPSCs and the organoids are identical except for the uncorrected gene mutation. The organoids were generated using the carbon fibers (CFs) as scaffolds in both D) and E). f) iPSCs and the organoids from ASD patients with Rab39b mutation, deletion of Cntnap2, GTF2I, BAZ1B, CLIP2, and EI4H, but no mutation corrected organoids were available currently. The panels described the key features of the organoids, and the panels showed the potential pathophysiological study and drug screenings.