Student Seminar on Nov 21, 2023





12:00-13:00, Nov 21, 2023


E203,Biomedicine Hall, Tsinghua University


Xinyu She(佘心宇)


Investigating the Pathogenic Mechanism of Type I Bipolar Disorder in iPSC-derived Brain Organoid Model


Type-I bipolar disorder (BDI) is a chronic, complex psychiatric disorder with an incidence of ~0.6-1.0%, however, the molecular mechanisms underlying BDI have remained largely elusive. Lithium (Li) is an effective and well-established mood stabilizer for BDI patients, although approximately 30-40% of patients fail to show positive response to Li. Due to the difficulties in directly analyzing the human brain, brain organoids derived from induced pluripotent stem cells (iPSCs) have emerged as a powerful tool for investigating the pathogenic mechanisms of BDI. To explore the midbrain pathogenic mechanisms of BDI and mechanisms of lithium response, we differentiated iPSC-derived midbrain organoids from 4 healthy controls and 6 BDI patients (3 Li responders, LR, and 3 Li non-responders, NR). We observed the widespread transcriptional dysregulation and aberrant cell composition in BDI midbrain organoids. Moreover, the expression of AQP4 was attenuated in BDI midbrain organoids, which may play a role in the mechanism of lithium response. Our findings provide molecular insights into the pathogenesis of BDI and mechanisms of lithium response.