TRIPLE ASSEMBLOIDS TO MODEL CORTICO-STRIATAL AND NIGRO-STRIATAL CONNECTIVITY IN PARKINSON’S DISEASE
Paris Brain Institute
Presentation
Date TBA
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Poster Board
PS03-08AM-371
Poster
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To improve PD modelling, we developed a 3D human organoid system derived from induced pluripotent stem cells (iPSCs). This model integrates ventral midbrain organoids (VMO) representing DA neurons, ventral forebrain organoids (VFO) for striatal MSNs, and dorsal forebrain organoids (DFO) for cortical neurons, recreating key aspects of basal ganglia circuitry.
We confirmed DA neuron differentiation in VMOs, MSN markers (DARPP32) and GABA-expressing cells in VFOs, and glutamatergic cortical layers in DFOs by day 90. Enhanced maturation of DA neurons and cortical organization were observed, with DA and glutamatergic projections observed in VFO, in the vicinity of the MSNs.
Preliminary results using PRKN knock-out (KO) iPSCs, a gene linked to autosomal recessive PD, demonstrated altered calcium activity in VFO-VMO assembloids. These findings highlight the potential of this model to unravel mechanisms of DA neuron degeneration and basal ganglia circuit development in PD.
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