human stem cells

Generation of Natural Killer Cells from Human Expanded Potential Stem Cells

Untitled Seminar

Giordano Lippi – Beyond transcription – microRNA mechanisms of brain development; Maria Isabel Carreño-Muñoz– Role of GABAergic circuits in the generation of sensory processing dysregulations in SYNGAP1 haploinsufficiency; Rhys Knowles-TBA; Nigel Kee- That other half: Derivation of posterior axial tissues from human stem cells

Using Human Stem Cells to Uncover Genetic Epilepsy Mechanisms

Reprogramming somatic cells to a pluripotent state via the induced pluripotent stem cell (iPSC) method offers an increasingly utilized approach for neurological disease modeling with patient-derived cells. Several groups, including ours, have applied the iPSC approach to model severe genetic developmental and epileptic encephalopathies (DEEs) with patient-derived cells. Although most studies to date involve 2-D cultures of patient-derived neurons, brain organoids are increasingly being employed to explore genetic DEE mechanisms. We are applying this approach to understand PMSE (Polyhydramnios, Megalencephaly and Symptomatic Epilepsy) syndrome, Rett Syndrome (in collaboration with Ben Novitch at UCLA) and Protocadherin-19 Clustering Epilepsy (PCE). I will describe our findings of robust structural phenotypes in PMSE and PCE patient-derived brain organoid models, as well as functional abnormalities identified in fusion organoid models of Rett syndrome. In addition to showing epilepsy-relevant phenotypes, both 2D and brain organoid cultures offer platforms to identify novel therapies. We will also discuss challenges and recent advances in the brain organoid field, including a new single rosette brain organoid model that we have developed. The field is advancing rapidly and our findings suggest that brain organoid approaches offers great promise for modeling genetic neurodevelopmental epilepsies and identifying precision therapies.

Instrument-free single-cell resolution of transcriptome changes in human stem cells during accelerated neuronal development triggered by knocking out the amyloid precursor protein